A PRC2-Kdm5b axis sustains tumorigenicity of acute myeloid leukemia
Year: 2022
Type: article
Abstract: Significance Acute myeloid leukemias (AMLs) with NUP98-NSD1 or MLL abnormality are generally aggressive, demanding a better understanding of the underlying oncogenic mechanisms. We show that these AMLs rely on a regulatory axis involving PRC2 – | Kdm5b – |stemness genes for sustaining an oncogenic program. The H3K27 methylase activity of polycomb repressive complex 2 (PRC2) is crucial for repressing Kdm5b, a corepressor carrying a H3K4me3 reader domain, that antagonizes the AML oncoproteins by directly binding to and down-regulating the AML stemness genes, thereby suppressing acute leukemogenesis. Such an AML-suppressing role of Kdm5b is not dependent on its intrinsic demethylase activity but requires its scaffold and/or chromatin association functions. The findings of this study shall aid in potential therapeutics of the affected AML patients.
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Awards: G1940748766, G2470153857, G401400328, Mechanism and Targeting of Transcriptional Factor/Coactivator Interactions in B-Cell Maligancy, Mechanism of Msh6-Mediated Gene Transcripiton and Tumorigenesis in B-Cell Maliganancies, Targeting histone methyltransferase EZH2 for the treatment of hematological cancer, Cancer Center Support Grant
OpenAlex ID: W4214714880