Subclones with variants of uncertain clinical significance might contribute to ineffective hemopoiesis and leukemia predisposition.

Background: Splicing modifications, genomic instability, and hypomethylation are central mechanisms promoting myelodysplasia and acute myeloid leukemia (AML). In this real-life retrospective study, to elucidate pathophysiology of clonal hemopoiesis in hematological malignancies, we investigated clinical significance of mutations in leukemia-related genes of known pathogenetic significance and of variants of uncertain clinical significance (VUS) in a cohort of patients with MDS and AML.

Methods: A total of 59 consecutive subjects diagnosed with MDS, 48 with AML, and 17 with clonal cytopenia with unknown significance were screened for somatic mutations in AML-related genes by next-generation sequencing.

Clinical efficacy of azacytidine and venetoclax and prognostic impact of Tim-3 and galectin-9 in acute myeloid leukemia and high-risk myelodysplastic syndromes: A single-center real-life experience.

Treatment of acute myeloid leukemia (AML) and high-risk myelodysplastic syndromes (MDS) is difficult in older patients with comorbidities and high-risk disease factors. Venetoclax, the first-in-class Bcl-2 inhibitor, has proven efficacy and safety in combination with azacytidine for treatment of high-risk myeloid diseases. In this single-center real-life retrospective study, a total of 27 consecutive patients treated with azacytidine plus venetoclax were included, and clinical outcomes, hematological improvements, and biomarkers of responsiveness to therapy were compared to those observed in an historical cohort of 95 consecutive patients treated with azacytidine as single agent.

c-Kit M541L variant is related to ineffective hemopoiesis predisposing to clonal evolution in 3D in vitro biomimetic co-culture model of bone marrow niche.

Hematopoietic stem cell (HSC) maintenance is challenging because stem cell survival relies on cell-to-cell contacts and paracrine signals from bone marrow (BM) microenvironment. Indeed, HSCs easily differentiate in conventional culture systems, and study of stem cell biology, leukemogenesis, and evolutionary trajectories is limited. 3D-culture systems can mimic tissue architecture and microenvironment thus preserving HSC phenotype.

Efficacy of Decitabine and Venetoclax as Salvage and Bridge Therapy to Haploidentical Hematopoietic Stem Cell Transplantation in a Multiresistant Acute Myeloid Leukemia Patient.

Treatment of relapsed/refractory or elderly unfit acute myeloid leukemia (AML) is still challenging, and hypomethylating agents in combination with venetoclax, an oral selective BCL2 inhibitor, might be successfully used as salvage therapy. However, clinical trials evaluating the efficacy and safety of this combination in the setting of multiresistant AML treatment also as a bridge to transplant are still ongoing. Here, we reported a 50-year-old male diagnosed with AML with normal cytogenetics and wild type for fms-like tyrosine kinase 3, nucleophosmin 1, and KIT, and treated with decitabine and venetoclax as the fifth line of therapy and after a relapse post-allogeneic transplant.

Expression Levels Combined with Flow Cytometry Blast Counts for Risk Stratification of Acute Myeloid Leukemia and Myelodysplastic Syndromes.

Wilm's tumor 1 (), a zinc-finger transcription factor and an epigenetic modifier, is frequently overexpressed in several hematologic disorders and solid tumors, and it has been proposed as diagnostic and prognostic marker of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). However, the exact role of in leukemogenesis and disease progression remains unclear. In this real-world evidence retrospective study, we investigated prognostic role of WT1-mRNA expression levels in AML and MDS patients and correlations with complete blood counts, flow cytometry counts, and molecular features.

Prophylactic letermovir decreases cytomegalovirus reactivation after stem cell transplantation: a single-center real-world evidence study.

Cytomegalovirus (CMV) reactivation is a major cause of morbidity and mortality after organ or hematopoietic stem cell transplantation (HSCT). Letermovir (LTV) is a novel antiviral agent approved for CMV prophylaxis after allogeneic transplantation. In this single-center real-world study, we evidenced the efficacy and safety of LTV for CMV prophylaxis in allogeneic HSCT recipients.