Acquired aplastic anemia and severe congenital neutropenia (SCN) are bone marrow (BM) failure syndromes of different origin, however, they share a common risk for secondary leukemic transformation. Here, we present a patient with severe aplastic anemia (SAA) evolving to secondary chronic neutrophilic leukemia (CNL; SAA-CNL). We show that SAA-CNL shares multiple somatic driver mutations in CSF3R, RUNX1, and EZH2/SUZ12 with cases of SCN that transformed to myelodysplastic syndrome or acute myeloid leukemia (AML). This molecular connection between SAA-CNL and SCN progressing to AML (SCN-AML) prompted us to perform a comparative transcriptome analysis on nonleukemic CD34high hematopoietic stem and progenitor cells, which showed transcriptional profiles that resemble indicative of interferon-driven proinflammatory responses. These findings provide further insights in the mechanisms underlying leukemic transformation in BM failure syndromes.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7656927 | PMC |
| http://dx.doi.org/10.1182/bloodadvances.2020001541 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Treatment of Vietnamese patients diagnosed with myelodysplastic neoplasms: Practical experience in a developing country.
Leuk Res Rep
November 2024
Department of Chemotherapy, National Institute of Hematology and Blood Transfusion, Hanoi 11312, Vietnam.
Background: Treatment of patients diagnosed with myelodysplastic neoplasms (MDS) is difficult and the outcome is still limited, especially in developing countries. We conducted this study in order to share some experience in treating patients diagnosed with MDS in developing countries.
Methods: This was a retrospective study that included 32 patients with newly MDS.
Implications of Clonal Hematopoiesis in Hematological and Non-Hematological Disorders.
Cancers (Basel)
December 2024
Department of Medicine, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
Clonal hematopoiesis (CH) is associated with an increased risk of developing myeloid neoplasms (MNs) such as myelodysplastic neoplasm (MDS) and acute myeloid leukemia (AML). In general, CH comprises clonal hematopoiesis of indeterminate potential (CHIP) and clonal cytopenia of undetermined significance (CCUS). It is an age-related phenomenon characterized by the presence of somatic mutations in hematopoietic stem cells (HSCs) and hematopoietic stem and progenitor cells (HSPCs) that acquire a fitness advantage under selection pressure.
View Article and Find Full Text PDFA comparative retrospective study of pre-fibrotic primary myelofibrosis overtly fibrotic stage in Qatar: clinicopathological, genetic landscape, risk stratification and survival data (2008-2021) - a single center experience.
Hematology
December 2024
Department of Haematology and Bone Marrow Transplant, National Center for Cancer Care and Research (NCCCR), Hamad Medical Corporation, Doha, Qatar.
Article Synopsis
- This study presents the first extensive report on Primary Myelofibrosis (PMF) in Qatar, covering data collected over 13 years, as there is a significant lack of information about PMF in the MENA region.
- Findings show that pre-PMF patients differ from overt PMF patients in terms of blood counts and genetic features, with overt PMF having a higher risk category and worse disease progression.
- The research provides important insights into the importance of the DIPSS plus scoring system, highlighting its effectiveness in identifying high-risk patients who face worse outcomes and increased treatment needs.
Targeting chromatin modifying complexes in acute myeloid leukemia.
Stem Cells Transl Med
November 2024
Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, United States.
Article Synopsis
- Acute myeloid leukemia (AML) is a serious blood cancer characterized by frequent relapses, partly due to disruptions in chromatin modifications that affect cell behavior.
- Aberrant histone modifications lead to the activation of self-renewal genes in specific hematopoietic progenitor cells, which are crucial for the development of AML, particularly in cases with MLL rearrangements and NPM1 mutations.
- New research highlights how leukemic cells exploit histone modification complexes as potential treatment targets, and the review suggests combining therapies that inhibit these complexes to improve effectiveness and tackle resistance to current treatments.
Investigational drugs in early phase trials for myelofibrosis.
Expert Opin Investig Drugs
December 2024
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Introduction: Myelofibrosis (MF) is a chronic myeloproliferative neoplasm characterized by bone marrow fibrosis, cytopenias, and organomegaly. Four JAK inhibitors are US-FDA approved for treatment of MF. While these drugs reduce symptom burden and spleen size to varying degrees, they do not affect the natural disease course or decrease the risk of leukemic transformation.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!