Activation of GPR44 decreases severity of myeloid leukemia via specific targeting of leukemia initiating stem cells.

ABSTRACT: Relapse of acute myeloid leukemia (AML) remains a significant concern due to persistent leukemia-initiating stem cells (LICs) that are typically not targeted by most existing therapies. Using a murine AML model, human AML cell lines, and patient samples, we show that AML LICs are sensitive to endogenous and exogenous cyclopentenone prostaglandin-J (CyPG), Δ¹²-PGJ₂, and 15d-PGJ₂, which are increased upon dietary selenium supplementation via the cyclooxygenase-hematopoietic PGD synthase pathway. CyPGs are endogenous ligands for peroxisome proliferator-activated receptor gamma and GPR44 (CRTH2; PTGDR2). Deletion of GPR44 in a mouse model of AML exacerbated the disease suggesting that GPR44 activation mediates selenium-mediated apoptosis of LICs. Transcriptomic

SUBMITTER: Qian F 

PROVIDER: S-EPMC10428076 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature