Knockdown of let-7b in leukemia associated macrophages inhibit acute myeloid leukemia progression.

ABSTRACT

Macrophages, critical components of bone marrow microenvironment, are reported to be remodeled into leukemia-associated macrophages (LAMs) in leukemic microenvironment where they contribute to leukemia development, characterized as M2 macrophages with pro-tumor effects. However, how leukemic microenvironment transforms macrophages into LAMs remains unknown. Here, we analyzed the clinical relevance of LAMs and profiled their RNA-Seq from acute myeloid leukemia (AML) patients with complete remission (CR) after induction treatment and refractory AML patients. Our results showed that the proportion and number of LAMs in refractory AML patients was higher than that in CR patients and LAM was a poor prognostic factor of AML patients. Furthermore, let-7b was a potentially aberrant gene in LAMs contributed to M2-subtype characteristics. Knockdown of let-7b in LAMs could inhibit the development of AML by repolarizing LAMs toward M1-subtype characteristics through the activation of Toll-like receptor and NF-κB pathway. Our study provides insight for future LAM-based immunotherapy strategies for AML.