M2 macrophages drive leukemic transformation by imposing resistance to phagocytosis and improving mitochondrial metabolism.

ABSTRACT: It is increasingly becoming clear that cancers are a symbiosis of diverse cell types and tumor clones. Combined single-cell RNA sequencing, flow cytometry, and immunohistochemistry studies of the innate immune compartment in the bone marrow of patients with acute myeloid leukemia (AML) reveal a shift toward a tumor-supportive M2-polarized macrophage landscape with an altered transcriptional program, with enhanced fatty acid oxidation and NAD⁺ generation. Functionally, these AML-associated macrophages display decreased phagocytic activity and intra-bone marrow coinjection of M2 macrophages together with leukemic blasts strongly enhances in vivo transformation potential. A 2-day in vitro exposure to M2 macrophages results in the accumulation of CALR^low leukemic blast ce

SUBMITTER: Weinhauser I 

PROVIDER: S-EPMC11801312 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature