Introduction. Currently, there is no unequivocal opinion on the optimal list of studies for the genetic diagnosis of oncohematological disorders in children and adults. These discrepancies are due to the limited technological capabilities of laboratories, the rapid development of science, and a significant expansion of the range of new molecular markers, that are attractive, but only for a limited group of patients. Moreover, in modern conditions of limited access to resources, it seems important to bring desires, interests and opportunities to a common denominator.   Aim — to develop unified approaches to the cytogenetic and molecular genetic diagnosis of oncohematological diseases in children and adults based on the consensus opinion of the panel of experts.   Main findings. The review proposes the arrangement of cytogenetic and molecular genetic diagnostic tests in oncohematological disorders in children and adults into 3 categories depending on the frequency of genetic aberrations, the study complexity and the prognostic impact. Based on this and taking into account the diagnosis and age of patients, the minimal and optimal lists of clinically significant parameters and research markers were identified. The basic preanalytical principles for conducting cytogenetic and molecular genetic studies in oncohematology are pointed out. A brief description of a conventional cytogenetic study and a polymerase chain reaction for the diagnosis of oncohematological diseases is given. The paper also focused on the need for reference diagnostics of cytogenetic and molecular genetic studies in oncohematology. The article is addressed to the specialists in the field of laboratory genetics, clinical laboratory diagnostics, but may also be of interest to hematologists, pediatric oncologists and doctors of related branches.

Introduction. At the initiative of the Russian Hematology Society, the research group for the study of idiopathic aplastic anemia has developed clinical recommendations for the diagnosis and treatment of idiopathic aplastic anemia.Aim: to standardize diagnostic and therapeutic approaches for the treatment of acquired aplastic anemia in Russia.Methods. The methodological approaches used are based on the principles of evidence-based medicine, based on the recommendations of the Russian council of experts on the diagnosis and treatment of patients with idiopathic aplastic anemia, Russian and international experience in managing patients, and the recommendations of the European group for the study of aplastic anemia.Results. A new revised and updated version of the national clinical guidelines is presented.Conclusion. These recommendations are intended for doctors of various specialties, health administrators, and medical school students.Conflict of interest: the authors declare no conflict of interest.Financial disclosure: this study did not have sponsorship.

Introduction. Over the past 5 years, signifi cant progress has been achieved in the treatment of patients with Ph-negative acute lymphoblastic leukemia (ALL). Treatment results were compared between two protocols of the Russian multicenter studies «ALL-2009» and «ALL-2016», in which multicomponent high-dose consolidation was not used. The principle of continuity of treatment was observed with modifi cation of doses of cytostatic drugs depending on the depth of cytopenia.Aim – to compare the 5-year results of two studies and to determine the factors of unfavorable prognosis in the treatment of patients with ALL.Materials and methods. The studies were performed from April 2009 to April 2016 (ALL-2009) and from April 2016 to September 2021 (ALL-2016), and 596 patients were included: 330 in ALL-2009 and 266 in ALL-2016. The analysis was performed in March 2022. The median age of patients in ALL-2009 was 28 years (15–55), in ALL-2016 – 32.5 years (18–55). Cytogenetic studies were performed in 242 patients in ALL-2009 (73.3 %) and 236 patients in ALL-2016 (88.7 %). Patients in the ALL-2016 protocol underwent a centralized assessment of minimal residual disease (MRD) by fl ow cytometry on protocol +70 day (after completion of two induction phases), +133 and +190 days. Transplantation of allogeneic stem hematopoietic cells was performed in 7 % of patients in ALL-2009 and in 9 % in ALL-2016.Results. Overall, relapse-free survival (OS, RFS) and the probability of relapse for a period of 3 years from the moment of inclusion of patients in a particular study were 59 %, 63 % and 23 % for ALL-2009, and for ALL-2016 – 64 %, 59 % and 22 %, respectively. For patients with B-cell precursor ALL, two cytogenetic risk groups were formed, in which long-term survival rates differed signifi cantly: the standard group (hyperploid set of chromosomes and normal karyotype) – OS 63 %, RFS 70 %, and high cytogenetic risk (any abnormal karyotype, except for hyperploidy) – OS 49 %, RFS 52 % (р = 0.001, р = 0.0014). In T-ALL, cytogenetic markers had no prognostic value, but the immunophenotype of early T-cell precursor turned out to be an important predictor of poor prognosis (the probability of relapse was 52 % compared with 15 % for all other immunophenotypic variants). According to the results of centralized monitoring of MRD, it was determined that for B-cell precursor ALL, the signifi cant negative factors are the high cytogenetic risk group and positive MRD status at +70 day, and for T-cells, the early immunophenotype and positive MRD status at +133 day.

The landscape of chromosomal aberrations in the tumor cells of the patients with B-ALL is diverse and can influence the outcome of the disease. Molecular karyotyping at the onset of the disease using chromosomal microarray (CMA) is advisable to identify additional molecular factors associated with the prognosis of the disease. Molecular karyotyping data for 36 patients with Ph-negative B-ALL who received therapy according to the ALL-2016 protocol are presented. We analyzed copy number alterations and their prognostic significance for CDKN2A/B, DMRTA, DOCK8, TP53, SMARCA2, PAX5, XPA, FOXE1, HEMGN, USP45, RUNX1, NF1, IGF2BP1, ERG, TMPRSS2, CRLF2, FGFR3, FLNB, IKZF1, RUNX2, ARID1B, CIP2A, PIK3CA, ATM, RB1, BIRC3, MYC, IKZF3, ETV6, ZNF384, PTPRJ, CCL20, PAX3, MTCH2, TCF3, IKZF2, BTG1, BTG2, RAG1, RAG2, ELK3, SH2B3, EP300, MAP2K2, EBI3, MEF2D, MEF2C, CEBPA, and TBLXR1 genes, choosing t(4;11) and t(7;14) as reference events. Of the 36 patients, only 5 (13.8%) had a normal molecular karyotype, and 31 (86.2%) were found to have various molecular karyotype abnormalities—104 deletions, 90 duplications or amplifications, 29 cases of cnLOH and 7 biallelic/homozygous deletions. We found that 11q22-23 duplication involving the BIRC3, ATM and MLL genes was the most adverse prognostic event in the study cohort.

Background. Multiple myeloma complicated by extramedullary plasmacytoma is an unfavorable variant of the disease. It remains unknown what triggers tumor transformation. The review presents literature data on the pathogenesis of extramedullary disease, as well as a clinical example of a comprehensive study of the tumor substrate.Aim. To study the molecular and biological characteristics of the tumor substrate of the bone marrow and extramedullary plasmacytoma using various research methods.Materials and methods. A 55-year-old patient was admitted to National Medical Research Center for Hematology with a diagnosis of multiple myeloma occurring with extramedullary plasmacytoma of the retroperitoneal space. dNA was isolated from samples of different localization (blood plasma, Cd138+ bone marrow cells, plasmacytoma and buccal epithelial cells). The profile of short tandem dNA repeats (STR) from the obtained samples was studied by multiplex polymerase chain reaction followed by fragment analysis. fluorescent in situ hybridization (fISH) of bone marrow Cd138+ cells was performed using various dNA probes. Comparative genomic hybridization on a microarray (arrayCGH) plasmacytoma dNA was also performed. The mutation profile of the KRAS, NRAS, BRAF genes was studied by Sanger sequencing in tumor samples of various localizations.Results. The induction therapy (vCd (bortezomib + cyclophosphamide + dexamethasone), vRd (bortezomib + lenalidomide + dexamethasone), daratumumab therapy) was ineffective, death occurred 4 months after the first clinical manifestations appeared. Comparison of STR markers of circulating cell-free tumor dNA (cfdNA), Cd138+ bone marrow cells, and plasmacytoma revealed the largest number of involved loci exactly in plasmacytoma’ dNA. A mutation in the NRAS gene was found only in plasmacytoma’ dNA. This indicates the presence of another clone of tumor cells in the extra-medullary plasmacytoma. Molecular karyotyping of plasmacytoma using the arrayCGH method revealed rearrangements of many chromosomes. 1p32.3 bi-allelic deletion, amplification of 1q21, 8q24/MyC rearrangements and del17p13 were confirmed by arrayCGH molecular karyotyping and fISH studies in bone marrow and plasmacytoma.Conclusion. A comprehensive molecular genetic study of the extramedullary plasmacytoma’ substrate is necessary to understand the pathogenesis mechanisms and, on this basis, to develop differentiated therapeutic approaches.