Histone Hypoacetylation-Driven CD9 Repression Arrests Differentiation and Evades Immunosurveillance in Pediatric Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is a genetically heterogeneous hematologic malignancy characterized by uncontrolled proliferation of myeloid progenitor cells accompanied by impaired terminal differentiation. Despite intensive treatment regimes, the clinical outcomes remain poor, underscoring the need t...

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Bibliographic Details
Published in:Blood 2021-11, Vol.138 (Supplement 1), p.3311-3311
Main Authors: Xu, Yaqun, Chan, Kathy, Fok, Siu Ping, Man, Toni Ki Fong, Li, Chi Kong, Leung, Kam Tong
Format: Article
Language:English
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Summary:Acute myeloid leukemia (AML) is a genetically heterogeneous hematologic malignancy characterized by uncontrolled proliferation of myeloid progenitor cells accompanied by impaired terminal differentiation. Despite intensive treatment regimes, the clinical outcomes remain poor, underscoring the need to decipher the underlying pathology and implement therapeutic interventions. Emerging evidence suggest myeloblasts could evolve machineries to evade T cell patrol and hinder immunotherapies. Here, we present a new mechanism driving immune escape in the context of pediatric AML, based on our discoveries of CD9 in hematopoietic stem cells (HSC; Leung et al, Blood, 2011) and acute lymphoblastic leukemia (ALL; Leung et al, Leukemia, 2020). We first examined CD9 expression and its prognostic impact in patient cohorts of childhood leukemia. The expression of cell surface CD9 on blasts of pediatric AML patients (13.2%, n=81) was significantly lower than that of pediatric ALL patients (90.4%, n=181, P
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2021-152503