Inflammatory mechanisms in the AML bone marrow niche: From pathogenesis to therapy.
TL;DR
This review summarizes the current knowledge on inflammatory cytokines and signaling pathways in AML, focusing on their mechanisms of action and implications for immune tolerance and clonal hematopoiesis and the emerging therapeutic strategies targeting these pathways to improve clinical outcomes for patients with AML.
Abstract
Acute myeloid leukemia (AML) is a highly aggressive hematologic malignancy in which inflammatory signaling plays a pivotal role in disease pathogenesis. The dysregulation of the cytokine network leads to an increased abundance of pro-inflammatory mediators, such as IL-1β, TNF-α and IL-6, relative to anti-inflammatory cytokines like TGF-β and CXCL12. This disbalance in cytokine levels is closely associated with tumor development and fosters a pro-tumorigenic microenvironment by facilitating leukemic cell proliferation, reducing survival rates, and promoting drug resistance. In addition, inflammatory cytokines have been shown to preferentially support hematopoietic stem and progenitor cell populations harboring mutations associated with clonal hematopoiesis. This review summarizes the current knowledge on inflammatory cytokines and signaling pathways in AML, focusing on: (i) their mechanisms of action and implications for immune tolerance and clonal hematopoiesis and (ii) the emerging therapeutic strategies targeting these pathways to improve clinical outcomes for patients with AML.