Acute myeloid leukemia induces protumoral p16INK4a-driven senescence in the bone marrow microenvironment.

ABSTRACT: Acute myeloid leukemia (AML) is an age-related disease that is highly dependent on the bone marrow (BM) microenvironment. With increasing age, tissues accumulate senescent cells, characterized by an irreversible arrest of cell proliferation and the secretion of a set of proinflammatory cytokines, chemokines, and growth factors, collectively known as the senescence-associated secretory phenotype (SASP). Here, we report that AML blasts induce a senescent phenotype in the stromal cells within the BM microenvironment and that the BM stromal cell senescence is driven by p16INK4a expression. The p16INK4a-expressing senescent stromal cells then feed back to promote AML blast survival and proliferation via the SASP. Importantly, selective elimination of p16INK4a⁺ senescent BM stromal ce

SUBMITTER: Abdul-Aziz AM 

PROVIDER: S-EPMC6356984 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature