9 research outputs found
P691: MULTIOMIC SINGLE-CELL APPROACH REVEALED CLONAL ARCHITECTURE OF KIT MUTATIONS IN CHRONIC MYELOMONOCYTIC LEUKAEMIA PATIENTS WITH/WITHOUT SYSTEMIC MASTOCYTOSIS
Integrative Analysis of Blast Phase Chronic Myelomonocytic Leukemia Reveals Distinct Transformation Phenotypes Predictive of Drug Response
Chronic myelomonocytic leukaemia stem cell transcriptomes anticipate disease morphology and outcome
Multiomic Single-Cell Sequencing Reveals Patterns of Disease Evolution and Acute Transformation in Chronic Myelomonocytic Leukaemia
S171: HIGHER MDMX EXPRESSION WAS ASSOCIATED WITH HYPOMETHYLATING AGENT RESISTANCE AND WORSE SURVIVAL IN MYELODYSPLASTIC SYNDROME PATIENTS, INFERRING IT A POTENTIAL THERAPEUTIC TARGET
P720: A BONE MARROW MICROENVIRONMENTAL CELL SIGNATURE SCORING SYSTEM INDEPENDENTLY PREDICTED SURVIVAL AND DRUG RESISTANCE IN CHRONIC MYELOMONOCYTIC LEUKAEMIA PATIENTS
Higher MDMX expression was associated with hypomethylating agent resistance and inferior survival in MDS patients, inferring it a potential therapeutic target
A three-gene leukaemic stem cell signature score is robustly prognostic in chronic myelomonocytic leukaemia
Loss of TET2 in human hematopoietic stem cells alters the development and function of neutrophils
Somatic mutations commonly occur in hematopoietic stem cells (HSCs). Some mutant clones outgrow through clonal hematopoiesis (CH) and produce mutated immune progenies shaping host immunity. Individuals with CH are asymptomatic but have an increased risk of developing leukemia, cardiovascular and pulmonary inflammatory diseases, and severe infections. Using genetic engineering of human HSCs (hHSCs) and transplantation in immunodeficient mice, we describe how a commonly mutated gene in CH, TET2, affects human neutrophil development and function. TET2 loss in hHSCs produce a distinct neutrophil heterogeneity in bone marrow and peripheral tissues by increasing the repopulating capacity of neutrophil progenitors and giving rise to low-granule neutrophils. Human neutrophils that inherited TET2 mutations mount exacerbated inflammatory responses and have more condensed chromatin, which correlates with compact neutrophil extracellular trap (NET) production. We expose here physiological abnormalities that may inform future strategies to detect TET2-CH and prevent NET-mediated pathologies associated with CH.</p