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Despite the approval of new drugs, the inclusion of -omics-derived data and the integration of machine learning in both the diagnostic and therapeutic process, the prognosis of acute myeloid leukemia (AML) remains dismal. The curative path is still aimed at achieving a successful allogeneic hematopoietic stem cell transplant (HSCT) in most patients. Nevertheless, access to this procedure is limited to eligible patients. Moreover, post-HSCT outcomes are influenced by AML heterogeneity and patient-related factors. The rise of venetoclax (VEN)-based combinations as standard of care in the treatment of older or unfit AML patients, together with their peculiar management profile, has led researchers to evaluate the feasibility of this approach in patients proceeding toward HSCT. We reviewed the available evidence to weigh up the advantages and pitfalls of this new therapeutic strategy. [ABSTRACT FROM AUTHOR]

Thus, the observed loss and replacement of the wild-type RUNX1 runt domain could cause loss of the above-cited RUNX1-DNA and RUNX1-protein interactions. In this regard, in many predisposition syndromes, the disease progression (AML or MDS) generally occurs through a stepwise process involving the loss of the remaining wild-type allele and acquisition of additional cooperating mutations, whereas others appear to maintain the wild-type allele [[13]]. Germline mutations in the I RUNX1 i gene define a familial platelet disorder with a predisposition to myeloid malignancy (FPDMM). [Extracted from the article]

BCR-ABL1 and JAK2 V617F coexistence in myeloproliferative neoplasms has been described as concomitant or sequential events. Despite this, we present a unique case of chronic myeloid leukemia (CML) not referable to either of the known scenarios. BCR-ABL1 molecular monitoring was performed by real-time quantitative PCR (RQ-PCR). At the time of molecular relapse, a targeted next-generation sequencing analysis with a customized panel of 26 genes commonly mutated in myeloid diseases was performed. To investigate the kinetics of the JAK2 variant and its association with the BCR-ABL1 rearrangement, RQ-PCR was performed at different time points during the patient's follow-up. While negative at CML diagnosis, the JAK2 mutation was first detected 9 years later (VAF: 7.2%). The mutational burden of JAK2 remained stable in multiple determinations, with minor fluctuations independent of BCR-ABL1 kinetics. At the last available time point, the patient was in deep molecular response (MR4), the JAK2 mutational burden was 7%, and no clinical-laboratory findings of Ph-MPN were detectable. In the presented case, the JAK2variantoccurring during the course of the disease seems to stay in the shadows of CML, just as a bystander. The impact of this event (that may be considered suggestive of clonal hematopoiesis of indeterminate potential) on the disease outcome, even if seemingly irrelevant, has still to be explored. [ABSTRACT FROM AUTHOR]

The understanding of clonal hematopoiesis (CH) and its features is rapidly evolving in step with the spread of sequencing techniques. Indeed, CH detection is now an emerging aspect in clinical practice. The awareness of CH intersects with consolidated diagnostic paths, thus exposing 'grey zone' circumstances under the magnifying lens of clinicians. The interpretation of genomic data poses, in some cases, a true clinical challenge, sometimes further complicating the route to diagnosis. The line separating different entities is thin. The present work aims to review some of these challenging situations to help clinicians keep their balance along this tightrope. [ABSTRACT FROM AUTHOR]

Acute promyelocytic leukemia (APL) patients carry in 27% of cases an activating mutation of the fms-like tyrosine kinase-3 (FLT3) gene: internal tandem duplication (ITD) or tyrosine kinase domain (TKD) point mutation. The simultaneous presence of both types of mutations, so-called FLT3 dual mutations, has been reported in 2% of APL, but this circumstance has never been studied. We studied a cohort of 74 APL cases, performing an in-depth analysis of three FLT3 dual mutant cases. Nanopore sequencing (NS) allowed us to characterize their complex mutational profile, showing the occurrence of multiple activating FLT3 mutations on different alleles in the leukemic promyelocytes and suggesting a cumulative impact of these events on the constitutive activation of the FLT3 pathway in APL cells. NS approach not only sheds light on the FLT3 mutational complexity in APL, but may also be useful to better clarify the FLT3 mutations landscape in acute myeloid leukemia. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 66-year-old male patient with myelodysplastic syndrome (MDS) bearing a t(3;9)(q21.2;p24.3) gene rearrangement. The article adds that gene reciprocal translocation led to acute myeloid leukemia (AML) and the patient was administered with 5-azacytidine (AZA) and needed no red cell transfusion. Other topics include chromosomal translocation, zinc-finger proteins, and reciprocal fusion genes.

A letter to the editor is presented regarding the case of a 63-year-old man with leukocytosis and thrombocytopenia, and has been diagnosed with atypical chronic myeloid leukemia (aCML).

The article presents a case study of a 83-year-old male with acute myeloid leukemia (ALL) showing down-regulated BCOR gene expression referred to the University of Bari's Department of Emergency and Organ Transplantation (D.E.T.O.) in Italy for pancytopenia and hyperpyrexia. Topics include BCL6 corepressor gene dysregulation due to chromosomal translocation, chromosomal analysis via fluorescence in situ hybridization (FISH), and the dislocation of long intergenic non-coding RNAs (lncRNAs).