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Dr. Andrey Sudarikov
National Research Center for Hematology

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Research Keywords & Expertise

0 Immunogenetics
0 Sequence Analysis
0 Lymphoproliferative disorders
0 Hematological Oncology
0 Molecular diagnosis and genotyping

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Journal article
Published: 20 July 2021 in Viruses
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Lymphopenia is a frequent hematological manifestation, associated with a severe course of COVID-19, with an insufficiently understood pathogenesis. We present molecular genetic immunohistochemical, and electron microscopic data on SARS-CoV-2 dissemination and viral load (VL) in lungs, mediastinum lymph nodes, and the spleen of 36 patients who died from COVID-19. Lymphopenia <1 × 109/L was observed in 23 of 36 (63.8%) patients. In 12 of 36 cases (33%) SARS-CoV-2 was found in lung tissues only with a median VL of 239 copies (range 18–1952) SARS-CoV-2 cDNA per 100 copies of ABL1. Histomorphological changes corresponding to bronchopneumonia and the proliferative phase of DAD were observed in these cases. SARS-CoV-2 dissemination into the lungs, lymph nodes, and spleen was detected in 23 of 36 patients (58.4%) and was associated with the exudative phase of DAD in most of these cases. The median VL in the lungs was 12,116 copies (range 810–250281), lymph nodes—832 copies (range 96–11586), and spleen—71.5 copies (range 0–2899). SARS-CoV-2 in all cases belonged to the 19A strain. A immunohistochemical study revealed SARS-CoV-2 proteins in pneumocytes, alveolar macrophages, and bronchiolar epithelial cells in lung tissue, sinus histiocytes of lymph nodes, as well as cells of the Billroth pulp cords and spleen capsule. SARS-CoV-2 particles were detected by transmission electron microscopy in the cytoplasm of the endothelial cell, macrophages, and lymphocytes. The infection of lymphocytes with SARS-CoV-2 that we discovered for the first time may indicate a possible link between lymphopenia and SARS-CoV-2-mediated cytotoxic effect.

ACS Style

Adhamjon Abdullaev; Akmaljon Odilov; Maxim Ershler; Alexey Volkov; Tatiana Lipina; Tatiana Gasanova; Yuri Lebedin; Igor Babichenko; Andrey Sudarikov. Viral Load and Patterns of SARS-CoV-2 Dissemination to the Lungs, Mediastinal Lymph Nodes, and Spleen of Patients with COVID-19 Associated Lymphopenia. Viruses 2021, 13, 1410 .

AMA Style

Adhamjon Abdullaev, Akmaljon Odilov, Maxim Ershler, Alexey Volkov, Tatiana Lipina, Tatiana Gasanova, Yuri Lebedin, Igor Babichenko, Andrey Sudarikov. Viral Load and Patterns of SARS-CoV-2 Dissemination to the Lungs, Mediastinal Lymph Nodes, and Spleen of Patients with COVID-19 Associated Lymphopenia. Viruses. 2021; 13 (7):1410.

Chicago/Turabian Style

Adhamjon Abdullaev; Akmaljon Odilov; Maxim Ershler; Alexey Volkov; Tatiana Lipina; Tatiana Gasanova; Yuri Lebedin; Igor Babichenko; Andrey Sudarikov. 2021. "Viral Load and Patterns of SARS-CoV-2 Dissemination to the Lungs, Mediastinal Lymph Nodes, and Spleen of Patients with COVID-19 Associated Lymphopenia." Viruses 13, no. 7: 1410.

Journal article
Published: 15 July 2021 in Terapevticheskii arkhiv
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The prevalence of multiple primary tumors has significantly increased last time. The question of choosing the optimal tactics of therapy today not fully resolved. Particular interest is the simultaneous detection of two neoplasms of similar origin in one study biopsy material. This publication presents a case of simultaneous diagnosis of myeloid sarcoma and mantle cell lymphoma in a 65-year-old patient, which required use of two different chemotherapy protocols. This example shows the need to use an extended diagnostic approach at all stages of the therapy, which allows choosing right tactics of therapy and achieving complete remission of two neoplasms.

ACS Style

Olga A. Gavrilina; Vitalii S. Dubov; Vera V. Troitskaya; Alla M. Kovrigina; Valentina N. Dvirnyk; Irina V. Galtseva; Andrei B. Sudarikov; Tatiana N. Obukhova; Elena N. Parovichnikova; Valerii G. Savchenko. Multiple primary tumor of hematopoietic tissue: myeloid sarcoma in combination with mantle cell lymphoma. Case report. Terapevticheskii arkhiv 2021, 93, 793 -799.

AMA Style

Olga A. Gavrilina, Vitalii S. Dubov, Vera V. Troitskaya, Alla M. Kovrigina, Valentina N. Dvirnyk, Irina V. Galtseva, Andrei B. Sudarikov, Tatiana N. Obukhova, Elena N. Parovichnikova, Valerii G. Savchenko. Multiple primary tumor of hematopoietic tissue: myeloid sarcoma in combination with mantle cell lymphoma. Case report. Terapevticheskii arkhiv. 2021; 93 (7):793-799.

Chicago/Turabian Style

Olga A. Gavrilina; Vitalii S. Dubov; Vera V. Troitskaya; Alla M. Kovrigina; Valentina N. Dvirnyk; Irina V. Galtseva; Andrei B. Sudarikov; Tatiana N. Obukhova; Elena N. Parovichnikova; Valerii G. Savchenko. 2021. "Multiple primary tumor of hematopoietic tissue: myeloid sarcoma in combination with mantle cell lymphoma. Case report." Terapevticheskii arkhiv 93, no. 7: 793-799.

Journal article
Published: 15 July 2021 in Terapevticheskii arkhiv
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Aim. To analyze the results of treatment in patients with acute myeloid leukemia (AML) within protocols AML-17 and modified AML-17 (mOML-17) as part of two consecutive pilot studies in order to develop the best treatment strategy for AML patients aged below 60 years. Materials and methods. The study included 89 AML patients who were aged below 60 years and received treatment within the AML-17 and mOML-17 protocols. Cytogenetic and molecular genetic studies were performed in all patients. The presence of mutations in the FLT3, NPM1, CEBPa genes was assessed by fragment analysis. 35 patients underwent a study for mutTP53, mutRUNX1 using next generation sequencing (NGS). The minimum residual population of tumor cells was evaluated by multicolor flow cytometry. Statistical analysis was performed using the procedures of the SAS 9.3 package. Results. Complete remission (CR) was achieved in 89.7% of patients treated with intensive chemotherapy (CT) courses and in 52.4% of patients treated with low-dose CT courses. 8.8% of intensively treated patients were refractory to therapy, and 38% did not respond to low-dose exposure. The early mortality rate was 3%. The overall survival and disease-free 3-year survival for patients included in 2 consecutive studies was were 60% and 67%, respectively. The level of minimal residual disease (MRD) after the first course of induction CT was an important prognostic indicator. The three-year relapse-free survival for patients in whom CR was achieved after the first course of induction CT and in whom MRD was not detected (MRD-negative status was obtained) was 90% compared to 43% for patients who were MRD positive after the first course of induction CT (p=0.00001). Conclusion. The key factor that significantly affects the long-term results of therapy is the rate of MRD after the first course of induction CT.

ACS Style

Elena N. Parovichnikova; Irina A. Lukianova; Vera V. Troitskaya; Mikhail Yu. Drokov; Larisa A. Kuzmina; Andrei N. Sokolov; Alina V. Kokhno; Zalina T. Fidarova; Irina V. Galtseva; Yuliya O. Davydova; Anastasiia I. Kashlakova; Elena O. Gribanova; Eugene E. Zvonkov; Elena P. Sysoeva; Valentina N. Dvirnyk; Tatiana N. Obukhova; Andrei B. Sudarikov; Yuliya V. Sidorova; Sergei M. Kulikov; Yuliia A. Chabaeva; Valerii G. Savchenko. Development of program therapy for patients with acute myeloid leukemia under the age of 60 years, based on the principles of differentiated effects. Terapevticheskii arkhiv 2021, 93, 753 -762.

AMA Style

Elena N. Parovichnikova, Irina A. Lukianova, Vera V. Troitskaya, Mikhail Yu. Drokov, Larisa A. Kuzmina, Andrei N. Sokolov, Alina V. Kokhno, Zalina T. Fidarova, Irina V. Galtseva, Yuliya O. Davydova, Anastasiia I. Kashlakova, Elena O. Gribanova, Eugene E. Zvonkov, Elena P. Sysoeva, Valentina N. Dvirnyk, Tatiana N. Obukhova, Andrei B. Sudarikov, Yuliya V. Sidorova, Sergei M. Kulikov, Yuliia A. Chabaeva, Valerii G. Savchenko. Development of program therapy for patients with acute myeloid leukemia under the age of 60 years, based on the principles of differentiated effects. Terapevticheskii arkhiv. 2021; 93 (7):753-762.

Chicago/Turabian Style

Elena N. Parovichnikova; Irina A. Lukianova; Vera V. Troitskaya; Mikhail Yu. Drokov; Larisa A. Kuzmina; Andrei N. Sokolov; Alina V. Kokhno; Zalina T. Fidarova; Irina V. Galtseva; Yuliya O. Davydova; Anastasiia I. Kashlakova; Elena O. Gribanova; Eugene E. Zvonkov; Elena P. Sysoeva; Valentina N. Dvirnyk; Tatiana N. Obukhova; Andrei B. Sudarikov; Yuliya V. Sidorova; Sergei M. Kulikov; Yuliia A. Chabaeva; Valerii G. Savchenko. 2021. "Development of program therapy for patients with acute myeloid leukemia under the age of 60 years, based on the principles of differentiated effects." Terapevticheskii arkhiv 93, no. 7: 753-762.

Journal article
Published: 15 July 2021 in Terapevticheskii arkhiv
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Background. LiFraumeni syndrome (LFS) is a rare, autosomal dominant, hereditary disorder that is characterized by an increased risk for certain types of cancer, acute lymphoblastic leukemia (ALL), particularly. Germline TP53 mutations are associated with LFS. Genetic counseling and follow-up is essential for patients with LFS and their relatives. Special therapeutic approaches are needed for treatment of oncological disease in these patients. The article presents a series of clinical cases of patients with ALL and SLF, considers general issues of diagnosis and treatment of adult patients with this hereditary genetic syndrome. Aim. Describe clinical observations of patients with acute lymphoblastic leukemia (ALL) and LFS and consider general issues of diagnosis and treatment of adult patients with LFS and ALL. Materials and methods. TP53 gene mutations were screened using Sanger sequencing in 180 de novo patients with Ph-negative (B- and T-cell) and Ph-positive ALL treated by Russian multicenter protocols (ALL-2009, ALL-2012, ALL-2016) at the National Research Center for Hematology, Moscow, Russia, and at the hematology departments of regional clinics of Russia (multicenter study participants). Results. TP53 gene mutations were found in 7.8% (n=14) of de novo ALL patients. In patients, whose biological material was available TP53 gene mutational status was determined in non-tumor cells (bone marrow and peripheral blood during remission, bone marrow samples after allogeneic hematopoietic stem cells transplantation and in tissue of non-hematopoietic origin) for discriminating germline mutations. The analysis included 5 patients (out of 14 with TP53 mutations), whose non-tumor biological material was available for research. Germline status was confirmed in 4 out of 5 B-cell ALL (n=3), T-cell ALL (n=1) investigated patients. Conclusion. Practical value of the research is the observation that the greater part of TP53 gene mutations in patients with Ph-negative B-cell ALL are germinal and associated with LFS.

ACS Style

Kseniia I. Zarubina; Elena N. Parovichnikova; Vadim L. Surin; Olesia S. Pshenichnikova; Olga A. Gavrilina; Galina A. Isinova; Vera V. Troitskaya; Andrei N. Sokolov; Irina V. Galtseva; Nikolai M. Kapranov; Juliia O. Davydova; Tatiana N. Obukhova; Elena E. Nikulina; Andrei B. Sudarikov; Valerii G. Savchenko. Li–Fraumeni syndrome in adult patients with acute lymphoblastic leukemia. Terapevticheskii arkhiv 2021, 93, 763 -769.

AMA Style

Kseniia I. Zarubina, Elena N. Parovichnikova, Vadim L. Surin, Olesia S. Pshenichnikova, Olga A. Gavrilina, Galina A. Isinova, Vera V. Troitskaya, Andrei N. Sokolov, Irina V. Galtseva, Nikolai M. Kapranov, Juliia O. Davydova, Tatiana N. Obukhova, Elena E. Nikulina, Andrei B. Sudarikov, Valerii G. Savchenko. Li–Fraumeni syndrome in adult patients with acute lymphoblastic leukemia. Terapevticheskii arkhiv. 2021; 93 (7):763-769.

Chicago/Turabian Style

Kseniia I. Zarubina; Elena N. Parovichnikova; Vadim L. Surin; Olesia S. Pshenichnikova; Olga A. Gavrilina; Galina A. Isinova; Vera V. Troitskaya; Andrei N. Sokolov; Irina V. Galtseva; Nikolai M. Kapranov; Juliia O. Davydova; Tatiana N. Obukhova; Elena E. Nikulina; Andrei B. Sudarikov; Valerii G. Savchenko. 2021. "Li–Fraumeni syndrome in adult patients with acute lymphoblastic leukemia." Terapevticheskii arkhiv 93, no. 7: 763-769.

Journal article
Published: 15 July 2021 in Terapevticheskii arkhiv
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Thrombotic complications are the most significant factors determining the prognosis in myeloproliferative neoplasms. Markers for assessing the risk of thrombosis are the number of leukocytes, platelets, hemoglobin level, hematocrit, age, molecular status, history of thrombosis, obesity, arterial hypertension, hyperlipidemia, hereditary or acquired thrombophilia. The pathogenesis of thrombosis in patients with myeloproliferative neoplasms is complex and multifactorial. In most cases, the etiological factor remains unknown. Currently, antiplatelet and anticoagulant therapy is carried out on an individual basis. The algorithm for primary and secondary (after thrombosis) prevention requires development and testing. We present a clinical case of repeated arterial and venous thrombotic complications in a patient with primary myelofibrosis.

ACS Style

Anait L. Melikyan; Irina N. Subortseva; Elena A. Gilyazitdinova; Tamara I. Koloshejnova; Kristina S. Shashkina; Elena K. Egorova; Alla M. Kovrigina; Andrei B. Sudarikov; Lana A. Gorgidze. Thrombosis in patients with myeloproliferative neoplasms. Case report. Terapevticheskii arkhiv 2021, 93, 800 -804.

AMA Style

Anait L. Melikyan, Irina N. Subortseva, Elena A. Gilyazitdinova, Tamara I. Koloshejnova, Kristina S. Shashkina, Elena K. Egorova, Alla M. Kovrigina, Andrei B. Sudarikov, Lana A. Gorgidze. Thrombosis in patients with myeloproliferative neoplasms. Case report. Terapevticheskii arkhiv. 2021; 93 (7):800-804.

Chicago/Turabian Style

Anait L. Melikyan; Irina N. Subortseva; Elena A. Gilyazitdinova; Tamara I. Koloshejnova; Kristina S. Shashkina; Elena K. Egorova; Alla M. Kovrigina; Andrei B. Sudarikov; Lana A. Gorgidze. 2021. "Thrombosis in patients with myeloproliferative neoplasms. Case report." Terapevticheskii arkhiv 93, no. 7: 800-804.

Journal article
Published: 07 June 2021 in Oncohematology
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Background. Genetic instability, an important phenomenon involved in oncogenic transformation and tumor progression, is associated with the insufficiency of the multicomponent DNA repair complex, in particular, the nucleotide mismatch repair (MMR) system. The MMR defect manifests itself as abnormalities in DNA microsatellite repeats, or microsatellite instability (MSI). In the studies of colorectal cancer, the role of MSI in prognostication of the disease, and defining the choice of specific therapy with immune checkpoint inhibitors has been proven. However, in lymphatic system tumors, the significance of this phenomenon is poorly understood. Determination of genetic instability in the onset of follicular lymphoma, a disease characterized by a heterogeneous course, may have prognostic value. Objective: to determine the genetic instability at the onset of follicular lymphoma. Materials and methods. Here we report an analysis of 24 microsatellite repeats and amelogenin loci in tumor cells of 46 follicular lymphoma patients. Results. In the studied cohort, lesions in microsatellite repeats were presented by MSI in 9 cases (19.6 %) and the loss of heterozygosity (LOH) in 19 cases (41.3 %). Most frequent lesions were found for the SE33 marker located at the q14 locus of chromosome 6. A significant association was shown between MSI and the double-hit follicular lymphoma group with rearrangements of the MYC and BCL2/BCL6 genes. Conclusion. Thus, our data indicate that the MSI phenomenon might be involved in the pathogenesis of the lymphatic tumors and particularly follicular lymphoma. However further studies on the expanded cohorts of patients are required to define the possible prognostic value of MSI in lymphatic tumors.

ACS Style

K. A. Sychevskaya; S. K. Kravchenko; N. V. Risinskaya; А. Е. Misyurina; E. E. Nikulina; F. E. Babaeva; A. B. Sudarikov. Microsatellite instability (MSI, EMAST) in the pathogenesis of follicular lymphoma. Oncohematology 2021, 16, 56-69 .

AMA Style

K. A. Sychevskaya, S. K. Kravchenko, N. V. Risinskaya, А. Е. Misyurina, E. E. Nikulina, F. E. Babaeva, A. B. Sudarikov. Microsatellite instability (MSI, EMAST) in the pathogenesis of follicular lymphoma. Oncohematology. 2021; 16 (2):56-69.

Chicago/Turabian Style

K. A. Sychevskaya; S. K. Kravchenko; N. V. Risinskaya; А. Е. Misyurina; E. E. Nikulina; F. E. Babaeva; A. B. Sudarikov. 2021. "Microsatellite instability (MSI, EMAST) in the pathogenesis of follicular lymphoma." Oncohematology 16, no. 2: 56-69.

Journal article
Published: 12 April 2021 in Genes
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JAK2 (Janus kinase 2) V617F, CALR (Calreticulin) exon 9, and MPL (receptor for thrombopoietin) exon 10 mutations are associated with the vast majority of Ph-negative chronic myeloproliferative neoplasms (MPNs). These mutations affect sequential stages of proliferative signal transduction and therefore, after the emergence of one type of mutation, other types should not have any selective advantages for clonal expansion. However, simultaneous findings of these mutations have been reported by different investigators in up to 10% of MPN cases. Our study includes DNA samples from 1958 patients with clinical evidence of MPN, admitted to the National Research Center for Hematology for genetic analysis between 2016 and 2019. In 315 of 1402 cases (22.6%), CALR mutations were detected. In 23 of these 315 cases (7.3%), the JAK2 V617F mutation was found in addition to the CALR mutation. In 16 from 24 (69.6%) cases, with combined CALR and JAK2 mutations, V617F allele burden was lower than 1%. A combination of JAK2 V617F with MPL W515L/K was also observed in 1 out of 1348 cases, only. JAK2 allele burden in this case was also lower than 1%. Additional mutations may coexist over the low background of JAK2 V617F allele. Therefore, in cases of detecting MPNs with a low allelic load JAK2 V617F, it may be advisable to search for other molecular markers, primarily mutations in exon 9 of CALR. The load of the combined mutations measured at different time points may indicate that, at least in some cases, these mutations could be represented by different clones of malignant cells.

ACS Style

Tatiana Makarik; Adhamjon Abdullaev; Elena Nikulina; Svetlana Treglazova; Elena Stepanova; Irina Subortseva; Alla Kovrigina; Anait Melikyan; Sergei Kulikov; Andrey Sudarikov. Low JAK2 V617F Allele Burden in Ph-Negative Chronic Myeloproliferative Neoplasms Is Associated with Additional CALR or MPL Gene Mutations. Genes 2021, 12, 559 .

AMA Style

Tatiana Makarik, Adhamjon Abdullaev, Elena Nikulina, Svetlana Treglazova, Elena Stepanova, Irina Subortseva, Alla Kovrigina, Anait Melikyan, Sergei Kulikov, Andrey Sudarikov. Low JAK2 V617F Allele Burden in Ph-Negative Chronic Myeloproliferative Neoplasms Is Associated with Additional CALR or MPL Gene Mutations. Genes. 2021; 12 (4):559.

Chicago/Turabian Style

Tatiana Makarik; Adhamjon Abdullaev; Elena Nikulina; Svetlana Treglazova; Elena Stepanova; Irina Subortseva; Alla Kovrigina; Anait Melikyan; Sergei Kulikov; Andrey Sudarikov. 2021. "Low JAK2 V617F Allele Burden in Ph-Negative Chronic Myeloproliferative Neoplasms Is Associated with Additional CALR or MPL Gene Mutations." Genes 12, no. 4: 559.

Journal article
Published: 30 March 2021 in Russian Clinical Laboratory Diagnostics
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Analysis of microsatellite instability (MSI) is a routine study in the diagnostics of solid malignancies. The standard for determining MSI is a pentaplex PCR panel of mononucleotide repeats: NR-21, NR-24, NR-27, BAT-25, BAT-26. The presence of MSI is established based on differences in the length of markers in the tumor tissue and in the control, but due to the quasimonomorphic nature of standard mononucleotide loci the use of a control sample is not necessary in the diagnosis of MSI-positive solid tumors. The significance of the MSI phenomenon in oncohematology has not been established. This paper presents the results of a study of MSI in B-cell lymphomas: follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), high-grade B-cell lymphoma (HGBL). We have shown that aberrations of mononucleotide markers occur in these diseases, but the nature of the changes does not correspond to the classical MSI in solid neoplasms. This fact requires further study of the pathogenesis of such genetic disorders. Due to the possibility of ambiguous interpretation of the results of the MSI study for previously uncharacterized diseases, strict compliance with the methodology of parallel analysis of the tumor tissue and the control sample is mandatory.

ACS Style

Kseniia Andreevna Sychevskaya; N. V. Risinskaya; S. K. Kravchenko; E. E. Nikulina; A. E. Misyurina; A. U. Magomedova; A. B. Sudarikov. Pitfalls in mononucleotide microsatellite repeats instability assessing (MSI) in the patients with B-cell lymphomas. Russian Clinical Laboratory Diagnostics 2021, 66, 181 -186.

AMA Style

Kseniia Andreevna Sychevskaya, N. V. Risinskaya, S. K. Kravchenko, E. E. Nikulina, A. E. Misyurina, A. U. Magomedova, A. B. Sudarikov. Pitfalls in mononucleotide microsatellite repeats instability assessing (MSI) in the patients with B-cell lymphomas. Russian Clinical Laboratory Diagnostics. 2021; 66 (3):181-186.

Chicago/Turabian Style

Kseniia Andreevna Sychevskaya; N. V. Risinskaya; S. K. Kravchenko; E. E. Nikulina; A. E. Misyurina; A. U. Magomedova; A. B. Sudarikov. 2021. "Pitfalls in mononucleotide microsatellite repeats instability assessing (MSI) in the patients with B-cell lymphomas." Russian Clinical Laboratory Diagnostics 66, no. 3: 181-186.

Journal article
Published: 11 March 2021 in Blood
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Chronic lymphocytic leukemia (CLL) is characterized by the existence of subsets of patients with (quasi)identical, stereotyped B-cell receptor (BcR) immunoglobulins. Patients in certain major stereotyped subsets often display remarkably consistent clinicobiological profiles, suggesting that the study of BcR immunoglobulin stereotypy in CLL has important implications for understanding disease pathophysiology and refining clinical decision-making. Nevertheless, several issues remain open, especially pertaining to the actual frequency of BcR immunoglobulin stereotypy and major subsets, as well as the existence of higher-order connections between individual subsets. To address these issues, we investigated clonotypic IGHV-IGHD-IGHJ gene rearrangements in a series of 29 856 patients with CLL, by far the largest series worldwide. We report that the stereotyped fraction of CLL peaks at 41% of the entire cohort and that all 19 previously identified major subsets retained their relative size and ranking, while 10 new ones emerged; overall, major stereotyped subsets had a cumulative frequency of 13.5%. Higher-level relationships were evident between subsets, particularly for major stereotyped subsets with unmutated IGHV genes (U-CLL), for which close relations with other subsets, termed “satellites,” were identified. Satellite subsets accounted for 3% of the entire cohort. These results confirm our previous notion that major subsets can be robustly identified and are consistent in relative size, hence representing distinct disease variants amenable to compartmentalized research with the potential of overcoming the pronounced heterogeneity of CLL. Furthermore, the existence of satellite subsets reveals a novel aspect of repertoire restriction with implications for refined molecular classification of CLL.

ACS Style

Andreas Agathangelidis; Anastasia Chatzidimitriou; Katerina Gemenetzi; Veronique Giudicelli; Maria Karypidou; Karla Plevova; Zadie Davis; Xiao-Jie Yan; Sabine Jeromin; Christof Schneider; Lone Bredo Pedersen; Renee C. Tschumper; Lesley-Ann Sutton; Panagiotis Baliakas; Lydia Scarfò; Ellen J. van Gastel; Marine Armand; Eugen Tausch; Bella Biderman; Constance Baer; Davide Bagnara; Alba Navarro; Anne Langlois de Septenville; Valentina Guido; Gerlinde Mitterbauer-Hohendanner; Aleksandar Dimovski; Christian Brieghel; Sarah Lawless; Manja Meggendorfer; Kamila Brazdilova; Matthias Ritgen; Monica Facco; Cristina Tresoldi; Andrea Visentin; Andrea Patriarca; Mark Catherwood; Lisa Bonello; Andrey Sudarikov; Katrina Vanura; Maria Roumelioti; Hana Skuhrova Francova; Theodoros Moysiadis; Silvio Veronese; Krzysztof Giannopoulos; Larry Mansouri; Teodora Karan-Djurasevic; Raphael Sandaltzopoulos; Csaba Bödör; Franco Fais; Arnon Kater; Irina Panovska; Davide Rossi; Salem Alshemmari; Panagiotis Panagiotidis; Paul Costeas; Blanca Espinet; Darko Antic; Letizia Foroni; Marco Montillo; Livio Trentin; Niki Stavroyianni; Gianluca Gaidano; Paola Francia di Celle; Carsten Niemann; Elias Campo; Achilles Anagnostopoulos; Christiane Pott; Kirsten Fischer; Michael Hallek; David Oscier; Stephan Stilgenbauer; Claudia Haferlach; Diane Jelinek; Nicholas Chiorazzi; Sarka Pospisilova; Marie-Paule Lefranc; Sofia Kossida; Anton W. Langerak; Chrysoula Belessi; Frederic Davi; Richard Rosenquist; Paolo Ghia; Kostas Stamatopoulos. Higher-order connections between stereotyped subsets: implications for improved patient classification in CLL. Blood 2021, 137, 1365 -1376.

AMA Style

Andreas Agathangelidis, Anastasia Chatzidimitriou, Katerina Gemenetzi, Veronique Giudicelli, Maria Karypidou, Karla Plevova, Zadie Davis, Xiao-Jie Yan, Sabine Jeromin, Christof Schneider, Lone Bredo Pedersen, Renee C. Tschumper, Lesley-Ann Sutton, Panagiotis Baliakas, Lydia Scarfò, Ellen J. van Gastel, Marine Armand, Eugen Tausch, Bella Biderman, Constance Baer, Davide Bagnara, Alba Navarro, Anne Langlois de Septenville, Valentina Guido, Gerlinde Mitterbauer-Hohendanner, Aleksandar Dimovski, Christian Brieghel, Sarah Lawless, Manja Meggendorfer, Kamila Brazdilova, Matthias Ritgen, Monica Facco, Cristina Tresoldi, Andrea Visentin, Andrea Patriarca, Mark Catherwood, Lisa Bonello, Andrey Sudarikov, Katrina Vanura, Maria Roumelioti, Hana Skuhrova Francova, Theodoros Moysiadis, Silvio Veronese, Krzysztof Giannopoulos, Larry Mansouri, Teodora Karan-Djurasevic, Raphael Sandaltzopoulos, Csaba Bödör, Franco Fais, Arnon Kater, Irina Panovska, Davide Rossi, Salem Alshemmari, Panagiotis Panagiotidis, Paul Costeas, Blanca Espinet, Darko Antic, Letizia Foroni, Marco Montillo, Livio Trentin, Niki Stavroyianni, Gianluca Gaidano, Paola Francia di Celle, Carsten Niemann, Elias Campo, Achilles Anagnostopoulos, Christiane Pott, Kirsten Fischer, Michael Hallek, David Oscier, Stephan Stilgenbauer, Claudia Haferlach, Diane Jelinek, Nicholas Chiorazzi, Sarka Pospisilova, Marie-Paule Lefranc, Sofia Kossida, Anton W. Langerak, Chrysoula Belessi, Frederic Davi, Richard Rosenquist, Paolo Ghia, Kostas Stamatopoulos. Higher-order connections between stereotyped subsets: implications for improved patient classification in CLL. Blood. 2021; 137 (10):1365-1376.

Chicago/Turabian Style

Andreas Agathangelidis; Anastasia Chatzidimitriou; Katerina Gemenetzi; Veronique Giudicelli; Maria Karypidou; Karla Plevova; Zadie Davis; Xiao-Jie Yan; Sabine Jeromin; Christof Schneider; Lone Bredo Pedersen; Renee C. Tschumper; Lesley-Ann Sutton; Panagiotis Baliakas; Lydia Scarfò; Ellen J. van Gastel; Marine Armand; Eugen Tausch; Bella Biderman; Constance Baer; Davide Bagnara; Alba Navarro; Anne Langlois de Septenville; Valentina Guido; Gerlinde Mitterbauer-Hohendanner; Aleksandar Dimovski; Christian Brieghel; Sarah Lawless; Manja Meggendorfer; Kamila Brazdilova; Matthias Ritgen; Monica Facco; Cristina Tresoldi; Andrea Visentin; Andrea Patriarca; Mark Catherwood; Lisa Bonello; Andrey Sudarikov; Katrina Vanura; Maria Roumelioti; Hana Skuhrova Francova; Theodoros Moysiadis; Silvio Veronese; Krzysztof Giannopoulos; Larry Mansouri; Teodora Karan-Djurasevic; Raphael Sandaltzopoulos; Csaba Bödör; Franco Fais; Arnon Kater; Irina Panovska; Davide Rossi; Salem Alshemmari; Panagiotis Panagiotidis; Paul Costeas; Blanca Espinet; Darko Antic; Letizia Foroni; Marco Montillo; Livio Trentin; Niki Stavroyianni; Gianluca Gaidano; Paola Francia di Celle; Carsten Niemann; Elias Campo; Achilles Anagnostopoulos; Christiane Pott; Kirsten Fischer; Michael Hallek; David Oscier; Stephan Stilgenbauer; Claudia Haferlach; Diane Jelinek; Nicholas Chiorazzi; Sarka Pospisilova; Marie-Paule Lefranc; Sofia Kossida; Anton W. Langerak; Chrysoula Belessi; Frederic Davi; Richard Rosenquist; Paolo Ghia; Kostas Stamatopoulos. 2021. "Higher-order connections between stereotyped subsets: implications for improved patient classification in CLL." Blood 137, no. 10: 1365-1376.

Perspective
Published: 03 March 2021 in Clinical Lymphoma Myeloma and Leukemia
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Background The use of standard therapy in HCL is often impossible at the time of deep neutropenia/agranulocytosis with or without infectious complications thus it is a complex therapeutic problem. Vemurafenib has been used to treat resistant HCL since 2012. As vemurafenib doesn't have a myelotoxic effect, we considered, that it can be used in the therapy of HCL in deep neutropenia/agranulocytosis with or without the development of infectious complications as a preliminary stage before treatment with cladribine. We conducted a retrospective analysis of treatment with vemurafenib of 22 patients in deep neutropenia/agranulocytosis with or without infectious complications at the diagnosis, followed by the standard course of cladribine. Patients and methods Vemurafenib was used in 22 patients with HCL. The response to therapy was evaluated by a complete blood cell count test (the absolute neutrophils count (ANC), hemoglobin concentration, platelets count, the absence of "hairy" cells), spleen size (with ultrasound examination), and reduce infectious complications. After there one standard course of the cladribine was used. Results Among the 22 patients, the ratio of men and female was 2:1; median age was 52 years (24-78 years), there were 7 patients with severe infectious manifestations admitted to the intensive care unit including 1 patient – during extracorporeal membrane oxygenation. The median of ANC at the diagnosis was 0.3 х 109/l (0.04 – 0.7 х 109/l). Vemurafenib was used in a dose of 240 mg 1-2 times a day. In 20 patients, vemurafenib was used for 3 months or more. In one case, the effect was not obtained during 1 month of treatment and the patient died from severe infectious complications during prolonged agranulocytosis. In 21 patients treated with vermurafenib, an increase of ANC was observed and the infectious complications were resolved, therefore allowing the application of cladribine therapy. After 1 standard course (0.1 mg/kg/day x 7 days) of cladribine chemotherapy, 18 (90%) patients achieved complete clinical remission and 2 (10%) patients achieved partial remission with residual splenomegaly. In 1 patient, vemurafenib therapy is currently ongoing (2 months from the start of therapy). Conclusion In cases with proven BRAFV600E mutation vemurafenib can be successfully used as an effective preliminary therapy in patients with deep neutropenia/agranulocytosis with or without infectious complications before standard therapy with purine analogs.

ACS Style

Svetlana Yu. Smirnova; Lyubov S. Al-Radi; Tatyana N. Moiseeva; Eduard G. Gemdzhian; Igor A. Yakutik; Hunan L. Julhakyan; Vyacheslav A. Novikov; Gennady M. Galstyan; Andrey B. Sudarikov. Inhibitor of BRAFV600E Mutation as a Treatment Option for Hairy Cell Leukemia With Deep Neutropenia and Infectious Complications. Clinical Lymphoma Myeloma and Leukemia 2021, 1 .

AMA Style

Svetlana Yu. Smirnova, Lyubov S. Al-Radi, Tatyana N. Moiseeva, Eduard G. Gemdzhian, Igor A. Yakutik, Hunan L. Julhakyan, Vyacheslav A. Novikov, Gennady M. Galstyan, Andrey B. Sudarikov. Inhibitor of BRAFV600E Mutation as a Treatment Option for Hairy Cell Leukemia With Deep Neutropenia and Infectious Complications. Clinical Lymphoma Myeloma and Leukemia. 2021; ():1.

Chicago/Turabian Style

Svetlana Yu. Smirnova; Lyubov S. Al-Radi; Tatyana N. Moiseeva; Eduard G. Gemdzhian; Igor A. Yakutik; Hunan L. Julhakyan; Vyacheslav A. Novikov; Gennady M. Galstyan; Andrey B. Sudarikov. 2021. "Inhibitor of BRAFV600E Mutation as a Treatment Option for Hairy Cell Leukemia With Deep Neutropenia and Infectious Complications." Clinical Lymphoma Myeloma and Leukemia , no. : 1.

Journal article
Published: 01 January 2021 in Clinical oncohematology
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Anait Levonovna Melikyan; A.M. Kovrigina; I.N. Subortseva; V.A. Shuvaev; E.V. Morozova; E.G. Lomaia; B.V. Afanasyev; T.A. Ageeva; V.V. Baikov; O.Yu. Vinogradova; S.V. Gritsaev; A.Yu. Zaritskey; T.I. Ionova; K.D. Kaplanov; I.S. Martynkevich; T.A. Mitina; E.S. Polushkina; T.I. Pospelova; M.A. Sokolova; A.B. Sudarikov; A.G. Turkina; Yu.V. Shatokhin; R.G. Shmakov; V.G. Savchenko. National Clinical Guidelines on Diagnosis and Treatment of Ph-Negative Myeloproliferative Neoplasms (Polycythemia Vera, Essential Thrombocythemia, and Primary Myelofibrosis) (Edition 2020). Clinical oncohematology 2021, 14, 1 .

AMA Style

Anait Levonovna Melikyan, A.M. Kovrigina, I.N. Subortseva, V.A. Shuvaev, E.V. Morozova, E.G. Lomaia, B.V. Afanasyev, T.A. Ageeva, V.V. Baikov, O.Yu. Vinogradova, S.V. Gritsaev, A.Yu. Zaritskey, T.I. Ionova, K.D. Kaplanov, I.S. Martynkevich, T.A. Mitina, E.S. Polushkina, T.I. Pospelova, M.A. Sokolova, A.B. Sudarikov, A.G. Turkina, Yu.V. Shatokhin, R.G. Shmakov, V.G. Savchenko. National Clinical Guidelines on Diagnosis and Treatment of Ph-Negative Myeloproliferative Neoplasms (Polycythemia Vera, Essential Thrombocythemia, and Primary Myelofibrosis) (Edition 2020). Clinical oncohematology. 2021; 14 (2):1.

Chicago/Turabian Style

Anait Levonovna Melikyan; A.M. Kovrigina; I.N. Subortseva; V.A. Shuvaev; E.V. Morozova; E.G. Lomaia; B.V. Afanasyev; T.A. Ageeva; V.V. Baikov; O.Yu. Vinogradova; S.V. Gritsaev; A.Yu. Zaritskey; T.I. Ionova; K.D. Kaplanov; I.S. Martynkevich; T.A. Mitina; E.S. Polushkina; T.I. Pospelova; M.A. Sokolova; A.B. Sudarikov; A.G. Turkina; Yu.V. Shatokhin; R.G. Shmakov; V.G. Savchenko. 2021. "National Clinical Guidelines on Diagnosis and Treatment of Ph-Negative Myeloproliferative Neoplasms (Polycythemia Vera, Essential Thrombocythemia, and Primary Myelofibrosis) (Edition 2020)." Clinical oncohematology 14, no. 2: 1.

Journal article
Published: 10 December 2020 in Russian journal of hematology and transfusiology
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Introduction. Mutations in the TP53 gene in patients with mantle cell lymphoma (MCL TP53+) are associated with a low response to intensive chemotherapy (CT) and adverse outcomes. Allogeneic haematopoietic stem cells transplantation (allo-HSCT) is a curative approach in MCL-TP53+ patients.Aim. Efficacy and safety assessment of allo-HSCT in MCL-TP53+ patients.Main findings. During 2016–2020, allo-HSCT in MCL TP53+ was performed in three patients. Two of them were grafted from HLA-identical unrelated donors, and one — from a haploidentical donor. Pre-transplant conditioning was “fludarabine + treosulfan + melphalan” in one case, and “fludarabine + busulfan” — in the other two. In three patients, leukocyte and platelet counts were recovered at days +18 and +20, +17 and +21, +19 and +16 after allo-HSCT, respectively. Acute graft-versushost disease (aGVHD) was observed in all patients (grade I — in 2 patients, grade IV — in 1 patient). One patient developed chronic GVHD (cGVHD) of moderate grade. All three patients exhibited complete remission and 100% donor chimerism in allo-HSCT follow-up of 6, 15 and 40 months, respectively.

ACS Style

D. A. Koroleva; N. G. Gabeeva; M. Yu. Drokov; V. A. Vasilyeva; B. V. Biderman; S. V. Tsygankova; E. S. Bulygina; G. M. Galstyan; A. B. Sudarikov; T. N. Obukhova; Л. А. Кузьмина; E. E. Zvonkov; E. N. Parovichnikova; V. G. Savchenko. First experience of allogeneic haematopoietic stem cell transplantation in patients with mantle cell lymphoma with a mutation in the TP53 gene. Russian journal of hematology and transfusiology 2020, 65, 483-500 .

AMA Style

D. A. Koroleva, N. G. Gabeeva, M. Yu. Drokov, V. A. Vasilyeva, B. V. Biderman, S. V. Tsygankova, E. S. Bulygina, G. M. Galstyan, A. B. Sudarikov, T. N. Obukhova, Л. А. Кузьмина, E. E. Zvonkov, E. N. Parovichnikova, V. G. Savchenko. First experience of allogeneic haematopoietic stem cell transplantation in patients with mantle cell lymphoma with a mutation in the TP53 gene. Russian journal of hematology and transfusiology. 2020; 65 (4):483-500.

Chicago/Turabian Style

D. A. Koroleva; N. G. Gabeeva; M. Yu. Drokov; V. A. Vasilyeva; B. V. Biderman; S. V. Tsygankova; E. S. Bulygina; G. M. Galstyan; A. B. Sudarikov; T. N. Obukhova; Л. А. Кузьмина; E. E. Zvonkov; E. N. Parovichnikova; V. G. Savchenko. 2020. "First experience of allogeneic haematopoietic stem cell transplantation in patients with mantle cell lymphoma with a mutation in the TP53 gene." Russian journal of hematology and transfusiology 65, no. 4: 483-500.

Journal article
Published: 10 December 2020 in Russian journal of hematology and transfusiology
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Introduction. Acute myeloid leukaemia (AML) is associated with multiple driver mutations, which prognostic value remains understudied.Aim. Assessment of the frequency of mutations in various genes and their impact on acute myeloid leukaemia outcome in adults.Materials and methods. The study included 90 adult patients with newly diagnosed AML; 76 were aged under 60, 14 were 60 and more years old. Patients under 60 had chemotherapy (CT) “7+3” as induction, the elder cohort had variant low-dose CT with hypomethylating agents. The molecular genetic status of patients was determined using next-generation sequencing; the in-house gene panel included ASXL1, BCOR, DNMT3, FLT3, IDH1, IDH2, PIGA, RUNX1, SETBP1, SF3B1, SRSF2, TET2, TP53 and U2AF2.Results. Nucleotide substitutions were identified in genes DNMT3, TET2, TP53, SETBP1, BCOR, RUNX1, IDH2, IDH1, FLT3, U2AF2, SF3B1 in 57.8 % of the patients (n = 52), with 17.8 % (n = 16) having compound mutations in two or three genes. Treatment efficacy and long-term outcomes were assessed against age, ELN-2017 risk groups and mutations in genes TP53, RUNX1, IDH1, IDH2 and DNMT3. In the long term, a reliable variation was revealed in the overall survival (OS) rate with respect to mutations in genes TP53 and RUNX1. Patients with mutant TP53 had 30 % OS, those with the intact gene — 53.4 % (p = 0.0037). Similar results were obtained with RUNX1: mutations marked 20 % OS, intact patients had 54% OS (p = 0.0466).Conclusion. Mutations in genes FLT3-ITD, NPM1 and CEBPA are proxy to AML. However, a more accurate prognosis and optimal choice of therapy require detailed molecular profiling due to genetic heterogeneity of AML patients.

ACS Style

A. I. Kashlakova; E. N. Parovichnikova; B. V. Biderman; Y. V. Sidorova; Y. A. Chabaeva; V. V. Troitskaya; I. A. Lukianova; A. V. Kokhno; A. N. Sokolov; A. B. Sudarikov; T. N. Obukhova; V. G. Savchenko. Next-generation sequencing-based molecular genetic profiling in adults with acute myeloid leukaemia. Russian journal of hematology and transfusiology 2020, 65, 444-459 .

AMA Style

A. I. Kashlakova, E. N. Parovichnikova, B. V. Biderman, Y. V. Sidorova, Y. A. Chabaeva, V. V. Troitskaya, I. A. Lukianova, A. V. Kokhno, A. N. Sokolov, A. B. Sudarikov, T. N. Obukhova, V. G. Savchenko. Next-generation sequencing-based molecular genetic profiling in adults with acute myeloid leukaemia. Russian journal of hematology and transfusiology. 2020; 65 (4):444-459.

Chicago/Turabian Style

A. I. Kashlakova; E. N. Parovichnikova; B. V. Biderman; Y. V. Sidorova; Y. A. Chabaeva; V. V. Troitskaya; I. A. Lukianova; A. V. Kokhno; A. N. Sokolov; A. B. Sudarikov; T. N. Obukhova; V. G. Savchenko. 2020. "Next-generation sequencing-based molecular genetic profiling in adults with acute myeloid leukaemia." Russian journal of hematology and transfusiology 65, no. 4: 444-459.

Journal article
Published: 10 December 2020 in Russian journal of hematology and transfusiology
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Introduction. The advent of tyrosine kinase inhibitors (TKIs) in clinical practice drastically improved prognosis in patients with chronic myeloid leukaemia (CML). Adverse events of the TKI therapy and its high financial burden warrant the trend to gradually abandon this treatment. Aim. To assess the results of CML patient monitoring after the withdrawal of TKI therapy. Patients and methods. This prospective study included 98 chronic phase CML patients satisfying the criteria: any receiving of TKI therapy for ≥3 years; deep molecular response (DMR, BCR-ABL ≤ 0.01 % IS) during ≥ 2 years. The withdrawal was followed by quantitative BCR-ABL estimation performed monthly for the first 6 months of the survey, bimonthly for 1 year and every 3 months from the second year onwards. Therapy was resumed at a loss of major molecular response (MMR, BCR-ABL ≥ 0.1 % IS). Results. The MMR loss upon the TKI withdrawal was observed in 48 (49 %) patients. Survival without MMR loss was 52 % past 24 months since withdrawal, with a median of 35 months (23–52). The duration of therapy, MR and the MR depth at the time of withdrawal significantly correlated with a conserved post-therapy MMR. Gender, age, a Sokal risk group, type and line of TKI therapy at withdrawal, and imatinib resistance in history were not observed to significantly impact molecular relapse-free remission. MMR was recovered in all 48 patients with TKI therapy resumed in molecular relapse. In 65 % of the patients, adverse therapy events observed during treatment completely resolved by 6 months of post-therapy monitoring. Musculoskeletal pain (withdrawal syndrome, WS) was reported in 42 % patients in the post-therapeutic period, which did not lead to TKI resumption. The WS development correlated with an elder age and longer therapy prior to withdrawal. Conclusion. Molecular relapse-free survival in CML patients with treatment-free remission (TFR) is comparable to other published evidence. Monitoring safety during TFR is attested by the lack of disease progression and MMR recovery upon TKI resumption in all patients.

ACS Style

A. G. Turkina; A. N. Petrova; E. Yu. Chelysheva; O. A. Shukhov; O. N. Tsyba; A. K. Golenkov; L. L. Vysotskaia; A. V. Bykova; I. S. Nemchenko; G. A. Gusarova; O. M. Pospelova; M. A. Gurianova; I. S. Martynkevich; A. O. Abdullaev; A. B. Sudarikov; S. M. Kulikov; V. G. Savchenko. A prospective study of the monitoring of patients with chronic myeloid leukemia upon withdrawal of tyrosine kinase inhibitor therapy. Russian journal of hematology and transfusiology 2020, 65, 370-385 .

AMA Style

A. G. Turkina, A. N. Petrova, E. Yu. Chelysheva, O. A. Shukhov, O. N. Tsyba, A. K. Golenkov, L. L. Vysotskaia, A. V. Bykova, I. S. Nemchenko, G. A. Gusarova, O. M. Pospelova, M. A. Gurianova, I. S. Martynkevich, A. O. Abdullaev, A. B. Sudarikov, S. M. Kulikov, V. G. Savchenko. A prospective study of the monitoring of patients with chronic myeloid leukemia upon withdrawal of tyrosine kinase inhibitor therapy. Russian journal of hematology and transfusiology. 2020; 65 (4):370-385.

Chicago/Turabian Style

A. G. Turkina; A. N. Petrova; E. Yu. Chelysheva; O. A. Shukhov; O. N. Tsyba; A. K. Golenkov; L. L. Vysotskaia; A. V. Bykova; I. S. Nemchenko; G. A. Gusarova; O. M. Pospelova; M. A. Gurianova; I. S. Martynkevich; A. O. Abdullaev; A. B. Sudarikov; S. M. Kulikov; V. G. Savchenko. 2020. "A prospective study of the monitoring of patients with chronic myeloid leukemia upon withdrawal of tyrosine kinase inhibitor therapy." Russian journal of hematology and transfusiology 65, no. 4: 370-385.

Genes and disease
Published: 05 December 2020 in Rheumatology International
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T-cell large granular lymphocytic leukemia (T-LGLL) is a lymphoproliferative disorder characterized by a persistent increase in the number of large granular lymphocytes (LGLs), neutropenia, and splenomegaly. Clinical manifestations of T-LGLL in the setting of rheumatoid arthritis (RA) are often identical to those in which one would suspect Felty's syndrome (FS). These disorders are distinguished by the presence of T-cell clonality, which is present in T-LGLL but not in FS. Mutations in the signal transducer and activator of transcription 3 (STAT3) and 5b (STAT5b) genes can be used as molecular markers of T-LGLL, but their prevalence in FS is unknown. Eighty-one patients with RA and unexplained neutropenia or/and an increase in the number of LGLs above 2 × 109/L were stratified into RA-associated T-LGLL (N = 56) or FS (N = 25) groups based on the presence or absence of T-cell clonality. STAT3 and STAT5b gene mutations were assessed in each group by means of allele-specific polymerase chain reaction assays. Clinical, immunological, laboratory data and the results of immunophenotyping of blood and bone marrow lymphocytes were also evaluated. Mutations of the STAT3 gene and an increase in the number of LGLs above 2 × 109/L were detected in RA-associated T-LGLL, but not in FS (39% vs 0% and 21% vs 0%, respectively). Mutations in the STAT5b gene were not observed in either group. Expression of CD57, CD16, and CD5−/dim on CD3+CD8+ T-lymphocytes was observed in both RA-associated T-LGLL and FS. STAT3 gene mutations or LGL counts over 2 × 109/L in RA patients are indicative of T-LGLL.

ACS Style

Vadim Romanovich Gorodetskiy; Yulia Vladimirovna Sidorova; Natalia Alexandrovna Kupryshina; Vladimir Ivanovich Vasilyev; Natalya Alexandrovna Probatova; Natalya Valerievna Ryzhikova; Andrey Borisovich Sudarikov. Analysis of a single-institution cohort of patients with Felty's syndrome and T-cell large granular lymphocytic leukemia in the setting of rheumatoid arthritis. Rheumatology International 2020, 41, 147 -156.

AMA Style

Vadim Romanovich Gorodetskiy, Yulia Vladimirovna Sidorova, Natalia Alexandrovna Kupryshina, Vladimir Ivanovich Vasilyev, Natalya Alexandrovna Probatova, Natalya Valerievna Ryzhikova, Andrey Borisovich Sudarikov. Analysis of a single-institution cohort of patients with Felty's syndrome and T-cell large granular lymphocytic leukemia in the setting of rheumatoid arthritis. Rheumatology International. 2020; 41 (1):147-156.

Chicago/Turabian Style

Vadim Romanovich Gorodetskiy; Yulia Vladimirovna Sidorova; Natalia Alexandrovna Kupryshina; Vladimir Ivanovich Vasilyev; Natalya Alexandrovna Probatova; Natalya Valerievna Ryzhikova; Andrey Borisovich Sudarikov. 2020. "Analysis of a single-institution cohort of patients with Felty's syndrome and T-cell large granular lymphocytic leukemia in the setting of rheumatoid arthritis." Rheumatology International 41, no. 1: 147-156.

Journal article
Published: 21 September 2020 in Russian journal of hematology and transfusiology
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Introduction. The pathogenesis of myeloproliferative neoplasms is associated with the chimeric gene BCR-ABL1 or with one of the driver mutations in the genes JAK2, MPL and CALR (Calreticulin). However, the classifi cation of the World Health Organization lists no myeloid neoplasms with more than one driver genetic abnormality. Aim. To search for mutations in the genes JAK2, MPL and CALR in patients with BCR-ABL1-positive chronic myeloid leukemia (CML), as well as to evaluate the kinetics of the discovered mutations during tyrosine kinase inhibitor (TKI) therapy. Materials and methods. mRNA and DNA samples isolated from blood and bone marrow cells of 567 CML patients, who underwent periodic monitoring of the BCR-ABL1 transcript level over the 2012–2019 period were included in the study The BCR-ABL1 transcript level was determined using a highly sensitive quantitative real-time polymerase chain reaction. The mutations JAK2V617F and MPLW515L/K were detected using real-time quantitative allele-specifi c polymerase chain reaction. Mutations in the CALR gene were investigated using fragment analysis followed by Sanger sequencing. Results. The combination of the BCR-ABL1, JAK2 and CALR gene mutations among CML patients receiving TKIs was 1.23 % (7/567). Out of these, the combination of BCR-ABL1 with JAK2V617F and the combination of BCR-ABL1 with CALR gene mutations were detected in 0.88 % (5/567) and 0.35 % (2/567) of cases, respectively. During TKI therapy, in 5 out of 7 patients, the level of BCR-ABL1 reached major molecular response (MR). In 4 of these patients, the therapy was discontinued. These patients are currently in molecular remission. In the remaining 2 patients, major MR was not achieved, despite the use of second-generation TKI preparations. Conclusions. The combination of the BCR-ABL1 chimeric gene with gene mutations Jak2 or CALR was a rare event and amounted to 0.88 and 0.35 % of cases, respectively. The combination of BCR-ABL1 with Jak2V617F and CALR mutations does not always impede the achievement of major MR.

ACS Style

A. O. Abdullaev; E. A. Stepanova; T. V. Makarik; E. Y. Nikulina; S. A. Treglazova; S. R. Goryacheva; O. A. Shukhov; A. V. Bykova; Z. V. Tratsevskaya; A. L. Melikyan; A. M. Kovrigina; A. G. Turkina; A. B. Sudarikov. Frequency of coexistence and kinetics of the BCR-ABL1 transcript level and allele burden of JAK2V617F and CALR Type 1, 2 gene mutations in patients with chronic myeloid leukemia. Russian journal of hematology and transfusiology 2020, 65, 253 -280.

AMA Style

A. O. Abdullaev, E. A. Stepanova, T. V. Makarik, E. Y. Nikulina, S. A. Treglazova, S. R. Goryacheva, O. A. Shukhov, A. V. Bykova, Z. V. Tratsevskaya, A. L. Melikyan, A. M. Kovrigina, A. G. Turkina, A. B. Sudarikov. Frequency of coexistence and kinetics of the BCR-ABL1 transcript level and allele burden of JAK2V617F and CALR Type 1, 2 gene mutations in patients with chronic myeloid leukemia. Russian journal of hematology and transfusiology. 2020; 65 (3):253-280.

Chicago/Turabian Style

A. O. Abdullaev; E. A. Stepanova; T. V. Makarik; E. Y. Nikulina; S. A. Treglazova; S. R. Goryacheva; O. A. Shukhov; A. V. Bykova; Z. V. Tratsevskaya; A. L. Melikyan; A. M. Kovrigina; A. G. Turkina; A. B. Sudarikov. 2020. "Frequency of coexistence and kinetics of the BCR-ABL1 transcript level and allele burden of JAK2V617F and CALR Type 1, 2 gene mutations in patients with chronic myeloid leukemia." Russian journal of hematology and transfusiology 65, no. 3: 253-280.

Journal article
Published: 21 September 2020 in Russian journal of hematology and transfusiology
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Introduction. An unfavorable prognosis in chronic lymphocytic leukemia (CLL) is associated with unmutated status of rearranged IGHV genes. CLL is also characterized by a narrowing of the repertoire of IGHV genes and the formation of quasiidentical (stereotyped) receptors, which is probably associated with antigenic selection of the tumor B-cell clone in the pathogenesis of the disease. The HLA phenotype plays an important role in antigenic selection of B cells. On the other hand, the association of specifi c HLA alleles with various diseases has been described. Aim. To assess the frequencies of HLA alleles in CLL patients with unmutated IGHV genes and the most common stereotyped receptors (SARs). Materials and methods. The study included 100 CLL patients with unmutated IGHV genes - 50 with the most common stereotyped antigen receptors (SARs) and 50 with non-stereotyped antigenic receptors. Control group of healthy donors was also included. Results. Signifi cant differences in HLA-allele repertoire between this two groups of patients and groups of donors were found. B*18 allele group was found much more common in patients with SARs than in donors and in patients without SARs. HLA-B*39 was more frequent for patients with SARs compared to donors; in patients without SARs these alleles were not found. For all patients, the frequency of HLA-B*52 alleles was higher than for donors. HLA-C*12 allelic group was found more frequent in CLL patients than in donors. HLA-DRB1*15 in CLL patients with SARs was found twice as often as in healthy donors or patients without SARs, while HLA-DRB1*13, oppositely, was found twice as rare. HLA-DRB1*16 was signifi cantly more frequent in patients without SARs, compared with donors and the patients with SARs. No signifi cant differences were found in the HLA-A and HLA-DQB1 loci. Conclusion. The association of two HLA alleles with “unmutated” CLL and two others with CLL bearing prognostically unfavorable SARs was found. HLA typing of expanded samples of CLL patients with different prognosis and course of the disease will provide more information on the mechanisms of antigen selection in the pathogenesis of CLL and improve diagnostic and therapeutic approaches.

ACS Style

B. V. Biderman; Е. Б. Ликольд; A. R. Abdrakhimova; E. A. Leonov; E. G. Khamaganova; A. B. Sudarikov. HLA allele repertoire in Russian chronic lymphocytic leukemia patients with an unfavorable prognosis. Russian journal of hematology and transfusiology 2020, 65, 312-320 .

AMA Style

B. V. Biderman, Е. Б. Ликольд, A. R. Abdrakhimova, E. A. Leonov, E. G. Khamaganova, A. B. Sudarikov. HLA allele repertoire in Russian chronic lymphocytic leukemia patients with an unfavorable prognosis. Russian journal of hematology and transfusiology. 2020; 65 (3):312-320.

Chicago/Turabian Style

B. V. Biderman; Е. Б. Ликольд; A. R. Abdrakhimova; E. A. Leonov; E. G. Khamaganova; A. B. Sudarikov. 2020. "HLA allele repertoire in Russian chronic lymphocytic leukemia patients with an unfavorable prognosis." Russian journal of hematology and transfusiology 65, no. 3: 312-320.

Journal article
Published: 01 September 2020 in Terapevticheskii arkhiv
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Aim.This study conducted the possibilities of diffusion-weighted magnetic resonance imaging of the whole body diffusion WB-MRI (in comparison with positron emission tomography with computed tomography PET/CT) in assessing the volume and prevalence of the tumor, as well as determining bone marrow (BM) damage (for various cytological types) in the diagnosis and staging of the disease in patients with FL. Materials and methods.A prospective comparative search study included 15 patients (4 men and 11 women, with a median age of 53 years) with newly diagnosed FL. Patients have not received antitumor chemotherapy previously. After the diagnosis was established, all patients (with the blindness of both the cases themselves and some specialists regarding the results of other specialists) were examined by PET/CT and diffusion WB-MRI, after which a BM examination was performed (histological examination and determination of B-cell clonality in BM puncture by PCR). Using the diffusion WB-MRI method, the prevalence of tumor lesion (nodal and extranodal foci) in each patient was estimated, and the total tumor volume was calculated, BM lesion was detected, and BM lesion volume was calculated. For lesions of different localization, the measured diffusion coefficient (DC) of the diffusion WB-MRI and the standardized rate of accumulation of the radiopharmaceutical in tissues (SUV) of the PET/CT method were determined and compared with each other (for the same areas). Statistical analysis was performed using the estimate of agreement (by Cohens kappa coefficient and asymptotic test) of the results of the compared methods. Results.Estimates of the prevalence of tumor damage (lymph nodes and extranodal foci) using the diffusion WB-MRI and PET/CT methods were the same. High DC and SUV were observed in the peripheral lymph nodes, extranodal foci and bulky, low DC and SUV in the foci of BM. All 4 methods successfully determined BM damage, however, the diffusion WB-MRI had comparatively less negative results. The highest values of SUV and CD were noted in cases of the 3 grade of FL. Using the diffusion WB-MRI method, the prevalence of tumor lesion was assessed in each patient (nodal and extranodal foci were detected) and the total tumor volume was calculated, BM lesion detection was performed, and the volume of BM lesion was calculated. It is important to note that with the help of diffusion WB-MRI, it was possible to measure separately the total tumor volume (462025 cm3) and separately the volume of bulky (251358 cm3). The diffusion WB-MRI allowed us to differentiate the volume of tumor tissue (reduced as a result of treatment) and residual (fibrous-adipose) tissue in residual formations (which averaged 21% of the initial volume). The predictors of a poor antitumor response were the maximum SUV values (more than 14.0) and the minimum DC values (0.510-3mm2/s) in the BM foci. Conclusion.The diffusion WB-MRI allows for detailed visualization of BM lesions and surrounding soft tissues both in the debut of the FL and in the process of tracking the effectiveness of chemotherapy, which makes it possible to use it along with PET/CT. Diffusion WB-MRI allows to separately evaluate the volume of true tumor tissue and residual tissue. Cases of the 3 grade of FL (including the transformation of FL into diffuse B-large cell lymphoma) are isolated due to low DC values (and high SUV values) in the tumor tissue. BM foci of FL lesion also have (in comparison with nodal and extranodal foci) lower DC values. The predictors of a poor antitumor response were high (from 14.0 or more) SUV valuesin the tumor (and especially in bulky), and low (about 0.5103mm2/s) DC values of BM foci. The PET/CT and diffusion WB-MRI have proven to be reliable diagnostic tools for establishing the stage of FL and detecting BM damage. Diffusion WB-MRI for FL is an informative first-line diagnostic method that allows regular monitoring of the disease and early detection of foci of relapse and disease progression.

ACS Style

E. S. Nesterova; G. A. Yatsyk; N. S. Lutsik; S. K. Kravchenko; A. B. Sudarikov; I. V. Krasil‘Nikova; E. G. Gemdzhian; A. M. Kovrigina. Informativeness of whole-body diffusion-weighted magnetic resonance imaging and positron emission tomography with computed tomography in follicular lymphoma. Terapevticheskii arkhiv 2020, 92, 55 -62.

AMA Style

E. S. Nesterova, G. A. Yatsyk, N. S. Lutsik, S. K. Kravchenko, A. B. Sudarikov, I. V. Krasil‘Nikova, E. G. Gemdzhian, A. M. Kovrigina. Informativeness of whole-body diffusion-weighted magnetic resonance imaging and positron emission tomography with computed tomography in follicular lymphoma. Terapevticheskii arkhiv. 2020; 92 (7):55-62.

Chicago/Turabian Style

E. S. Nesterova; G. A. Yatsyk; N. S. Lutsik; S. K. Kravchenko; A. B. Sudarikov; I. V. Krasil‘Nikova; E. G. Gemdzhian; A. M. Kovrigina. 2020. "Informativeness of whole-body diffusion-weighted magnetic resonance imaging and positron emission tomography with computed tomography in follicular lymphoma." Terapevticheskii arkhiv 92, no. 7: 55-62.

Multicenter study
Published: 01 September 2020 in Terapevticheskii arkhiv
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Issue.The study of activating mutations (NRAS,KRAS,FLT3,JAK2,CRLF2genes) of RAS/RAF/MEK/ERK and JAK/STAT signaling pathways in B-cell acute lymphoblastic leukemia (B-ALL) in adult patients which are included in Russian multicenter clinical trials. Materials and methods.Within the multicenter study there were 119 adult patients included withde novoB-ALL. The study was considered as prospective and retrospective. The group withBCR-ABL1-negative B-ALL consisted of up to 93 patients (45 male and 48 female, at the age of 17 to 59, the median age 31), they were treated according to the protocols ALL-2009, ALL-2016. The median follow-up lasted for 19 months (1119). The group withBCR-ABL1-positive B-ALL with up to 26 patients (10 male and 16 female, at the age of 23 to 78, the median age 34 years) was included in the study as well. The treatment was carried out according to the protocols ALL-2009 and ALL-2012 in combination with tyrosine kinase inhibitors. The median follow-up lasted for 23 months (4120). The molecular analysis of activating mutations inNRAS,KRASgenes (RAS/RAF/MEK/ERK signaling pathway) andJAK2,CRLF2genes (JAK/STAT signaling cascade) was performed via Sanger sequencing. The internal tandem duplications (ITDs) inFLT3gene were studied by fragment analysis. The evaluation of CRLF2 expression was fulfilled via flow cytometry. Results.Activating mutations inNRAS,KRAS,FLT3genes were found in 22 (23.6%) patients withBCR-ABL1-negative B-ALL. In total, 23 mutations were revealed in theNRAS(n=9),KRAS(n=12), andFLT3(n=2) genes, according to statistics that was significantly more frequent than withBCR-ABL1-positive B-ALL, these genes mutations were not identified in patients (p=0.007). The frequency of mutations detection inKRASandNRASgenes in patients withBCR-ABL1-negative B-ALL was comparable as 12.9% (12 of 93) to 9.7% (9 of 93), respectively (p=0.488). One patient was simultaneously revealed 2 mutations in theKRASgene (in codons 13 and 61).FLT3-ITD mutations were detected in 3.5% (2 of 57) cases ofBCR-ABL1-negative B-ALL. In patients withBCR-ABL1-positive B-ALLFLT3-ITD mutations were not assessed. Violations in the JAK/STAT signaling cascade were detected in 4 (4.3%) patients withBCR-ABL1-negative B-ALL. They were represented by the missense mutations ofJAK2gene (n=3) and the overexpression of CRLF2 (n=2); in one patient were detected the overexpression of CRLF2 and a mutation inJAK2gene simultaneously. No mutations were found inCRLF2gene. In patients withBCR-ABL1-positive B-ALL noJAK2mutations were detected. As long as analyzing demographic and clinical laboratory parameters between groups of patients with and without mutations, there were no statistically significant differences obtained. In the analyzed groups of patients, long-term therapy results did not differentiate according to the mutations presence inNRAS,KRAS,FLT3,JAK2genes. Also, substantive differences were not shown in the rate of the negative status achievement of the minimum residual disease between patients with and without activating mutations in the control points of the protocol (on the 70th, 133rd and 190th days). Conclusion.NRAS,KRAS,FLT3,JAK2activating mutations do not affect the long-term results of the therapy and the rate of the negative status achievement of the minimum residual disease in patients withBCR-ABL1-negative B-ALL treated by the Russian multicenter clinical trials.

ACS Style

K. I. Zarubina; E. N. Parovichnikova; V. L. Surin; O. S. Pshenichnikova; O. A. Gavrilina; G. A. Isinova; V. V. Troitskaia; A. N. Sokolov; I. V. Gal’Tseva; N. M. Kapranov; Iu. O. Davydova; T. N. Obukhova; A. B. Sudarikov; V. G. Savchenko. Detection of activating mutations in RAS/RAF/MEK/ERK and JAK/STAT signaling pathways. Terapevticheskii arkhiv 2020, 92, 31 -42.

AMA Style

K. I. Zarubina, E. N. Parovichnikova, V. L. Surin, O. S. Pshenichnikova, O. A. Gavrilina, G. A. Isinova, V. V. Troitskaia, A. N. Sokolov, I. V. Gal’Tseva, N. M. Kapranov, Iu. O. Davydova, T. N. Obukhova, A. B. Sudarikov, V. G. Savchenko. Detection of activating mutations in RAS/RAF/MEK/ERK and JAK/STAT signaling pathways. Terapevticheskii arkhiv. 2020; 92 (7):31-42.

Chicago/Turabian Style

K. I. Zarubina; E. N. Parovichnikova; V. L. Surin; O. S. Pshenichnikova; O. A. Gavrilina; G. A. Isinova; V. V. Troitskaia; A. N. Sokolov; I. V. Gal’Tseva; N. M. Kapranov; Iu. O. Davydova; T. N. Obukhova; A. B. Sudarikov; V. G. Savchenko. 2020. "Detection of activating mutations in RAS/RAF/MEK/ERK and JAK/STAT signaling pathways." Terapevticheskii arkhiv 92, no. 7: 31-42.

Case reports
Published: 01 September 2020 in Terapevticheskii arkhiv
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Primary myelofibrosis is a myeloproliferative neoplasm that occurs de novo, characterized by clonal proliferation of stem cells, abnormal expression of cytokines, bone marrow fibrosis, hepatosplenomegaly as a result of extramedullary hematopoiesis, symptoms of tumor intoxication, cachexemia, peripheral blood leukoerythroblastosis, leukemic progression and low survival. Primary myelofibrosis is a chronic incurable disease. The aims of therapy: preventing progression, increasing overall survival, improving quality of life. The choice of therapeutic tactics is limited. Allogenic hematopoietic stem cell transplantation is the only method that gives a chance for a cure. The role of mutations in a number of genes in the early identification of candidates for allogeneic hematopoietic stem cell transplantation is being actively studied. The article describes the clinical case of the detection ofASXL1gene mutations in a patient with prefibrous primary myelofibrosis. The diagnosis was established on the basis of WHO criteria 2016. The examination revealed a mutation ofASXL1. Interferon alfa therapy is carried out, against the background of which clinico-hematological remission has been achieved. Despite the identified mutation, the patient is not a candidate for allogeneic hematopoietic stem cell transplantation. Given the unfavorable prognostic value of theASXL1mutation, the patient is subject to active dynamic observation and aggressive therapeutic tactics when signs of disease progression appear.

ACS Style

A. L. Melikyan; I. N. Subortseva; E. A. Gilyazitdinova; T. I. Koloshejnova; E. K. Egorova; E. I. Pustovaya; A. B. Sudarikov; A. O. Abdullaev; L. A. Gorgidze; D. I. Chebotarev. The prognostic value of ASXL1 mutation in primary myelofibrosis. Literature review and clinical case description. Terapevticheskii arkhiv 2020, 92, 95 -99.

AMA Style

A. L. Melikyan, I. N. Subortseva, E. A. Gilyazitdinova, T. I. Koloshejnova, E. K. Egorova, E. I. Pustovaya, A. B. Sudarikov, A. O. Abdullaev, L. A. Gorgidze, D. I. Chebotarev. The prognostic value of ASXL1 mutation in primary myelofibrosis. Literature review and clinical case description. Terapevticheskii arkhiv. 2020; 92 (7):95-99.

Chicago/Turabian Style

A. L. Melikyan; I. N. Subortseva; E. A. Gilyazitdinova; T. I. Koloshejnova; E. K. Egorova; E. I. Pustovaya; A. B. Sudarikov; A. O. Abdullaev; L. A. Gorgidze; D. I. Chebotarev. 2020. "The prognostic value of ASXL1 mutation in primary myelofibrosis. Literature review and clinical case description." Terapevticheskii arkhiv 92, no. 7: 95-99.