Acute myeloid leukemia (AML) in older unfit patients is a therapeutic challenge for clinical hematologists. We evaluated the efficacy and safety of a novel low-intensity regimen consisting of low-dose cytarabine and cladribine (LD-AC+cladribine) in first-line treatment of elderly (≥60 years) AML patients not eligible for intensive chemotherapy (IC) who had either the Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2 or the hematopoietic cell transplantation comorbidity index (HCT-CI) score ≥3. The induction phase included two cycles of LD-AC+cladribine. Patients who achieved at least partial remission (PR) received maintenance treatment with LD-AC alone. Overall, 117 patients with a median age of 70 years were enrolled. Adverse cytogenetics, ECOG PS ≥2 and HCT-CI score ≥3 was observed in 43.5%, 60%, and 58% of patients, respectively. The response rate (≥PR) was 54% (complete remission [CR], 32%; CR with incomplete hematologic recovery [CRi], 5%). A median overall survival (OS) was 21 and 8.8 months in CR/CRi and PR group, respectively. Advanced age (≥75 years) and adverse cytogenetics had a negative impact on OS. The 56-day mortality rate was 20.5%. In conclusion, LD-AC+cladribine is a beneficial therapeutic option with a predictable safety profile in elderly AML patients not eligible for IC.

MicroRNA (miRNA), a significant class of regulatory non-coding RNA (ncRNA), can regulate the expression of numerous protein-coding messenger RNAs (mRNAs). miRNA plays an important part in shaping the human transcriptome. So far, in the human genome, about 2500 miRNAs have been found. Acute myeloid leukemia (AML) belongs to a malignant clonal disorder of hematopoietic stem cells and is characterized by the uncontrolled clonal proliferation of abnormal progenitor cells in the bone marrow and blood. For the past several years, significant scientific attention has been attracted to the role of miRNAs in AML, since alterations in the expression levels of miRNAs may contribute to AML development. This review describes the main functions of non-coding RNA classes and presents miRNA biogenesis. This study aims to review recent reports about altered microRNA expression and their influence on AML cell survival, cell cycle, and apoptotic potential. Additionally, it summarizes the correlations between miRNAs and their target mRNAs in AML and outlines the role of particular miRNAs in AML subtypes according to ELN recommendations.

Introduction: The misbalance between a family of inhibitor of apoptosis proteins (IAP), regulated by the nuclear factor kappa B (NF-κB) and their natural antagonist second mitochondrial-derived activator of caspases/direct IAP binding protein with low pI (Smac/DIABLO) are important to biology of acute myeloid leukemia (AML).Material and methods: The aim of the study was to assess NF-κB and Smac/DIABLO proteins expression in blasts of 109 newly diagnosed AML patients using the multicolor flow cytometry and evaluate their influence on AML patients outcome.Results: Expression of NF-κB and of Smac/DIABLO proteins were found in 95% and 98% of the patients, respectively. A negative correlation between Smac/DIABLO and NF-κB was observed. Age < 60 years old as well as higher Smac/DIABLO expression were associated with a higher probability of complete response achievement in the multivariate analysis. Longer overall survival (OS) in the univariate and multivariate analyses was influenced by age < 60 years old, a favorable or intermediate-risk karyotype and high Smac/DIABLO expression. Additionally, in the survival analysis of the subgroups, the patients aged < 60 years old, with high Smac/DIABLO expression, lower NF-κB expression and < 50% of bone marrow blasts who were treated with standard treatment had better OS.Conclusions: Lower NF-κB and higher Smac/DIABLO expression may influence AML patients outcome.

Acute myeloid leukemia (AML) is a heterogeneous, highly malignant neoplasm. Apoptosis is a complex process executed by caspases and suppressed by the inhibitor of apoptosis (IAP) family. Neuronal apoptosis inhibitory protein (NAIP), IAP’s member, may play an exceptional role in the mechanisms of tumors’ resistance to chemotherapy. The aims of the study were to assess the expression of NAIP in leukemic blasts of AML patients using flow cytometry and to evaluate its influence on disease outcome. NAIP expression was found in 106 out of 108 patients. A higher complete response rate was associated with a low expression of NAIP, age < 60 yo, and white blood cell count < 20 G/L (p= 0.009,p= 0.033, andp= 0.076, respectively) in univariate analyses and a low NAIP expression and age < 60 yo (p= 0.025 andp= 0.013, respectively) in multivariate analyses. Longer overall survival (OS) in the univariate analysis was influenced by a low NAIP expression, age < 60 yo, and intensive chemotherapy (p= 0.033,p< 0.001, andp< 0.001, respectively). In the intensively treated group, better OS was observed in patients with age < 60 yo,de novoAML, and a low NAIP expression (p= 0.03,p= 0.024, andp= 0.07, respectively). In multivariate analysis, longer OS was associated with age < 60 yo (p= 0.009) andde novoAML (p= 0.007). In conclusion, we suggest that NAIP might play an adverse role in response to chemotherapy.

Background: Secondary acute promyelocytic leukemia (sAPL) is a very rare subtype of acute myeloid leukemia that develops following exposure to chemotherapy, radiotherapy, or immunosuppressive agents. The treatment results and survival outcomes of sAPL patients are still not precisely defined. Methods: A search of the Polish Adult Leukemia Group (PALG) database identified 29 cases of sAPL (median age 57 years; 62.1% female) among 437 APL patients (6.7%) diagnosed between 2006 and 2024. Each sAPL case was matched to a de novo APL patient by sex, age, year of diagnosis, and treatment protocol (LPA (Leucemia Promielocítica Aguda) 2005, LPA 2012, or LPA 2017). Results: All sAPL cases occurred following chemo- and/or radiotherapy, most commonly for breast cancer. The sAPL cases demonstrated higher CD15 expression than the de novo APL cases (median 27.6% vs. 7%, p = 0.04). The two groups exhibited comparable complete remission rates (82.8% sAPL vs. 75.9% de novo; p = 0.75) and early mortality rates (17.2% vs. 20.7%, p = 1.0). However, relapse-free survival was significantly shorter in sAPL (median 94.7 months vs. not reached; HR 7.23, 95% CI 1.63–32.02, p = 0.030), whereas overall survival did not differ significantly between groups. Multivariate analysis identified Eastern Cooperative Oncology Group performance status ≥3 and CD15 expression > 20% as independent predictors of inferior survival. Conclusions: These findings suggest that sAPL shares many clinical features with de novo APL but carries a higher risk of relapse, highlighting the need for further prospective studies and the potential implementation of tailored therapeutic strategies.