Knockdown of Let-7b in Leukemia Associated Macrophages Inhibit Acute Myeloid Leukemia Progression

Abstract

As critical components of bone marrow microenvironment, macrophages are significant players in supporting and maintaining hematopoiesis. Macrophages 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 clinical relevance of LAMs and profiled their RNA-Seq from acute myeloid leukemia (AML) patients achieved complete remission (CR) after induction treatment and refractory AML patients. Our results showed that the proportion of LAMs in refractory AML patients was higher than that in CR patients and LAM was a strong indicator of poor prognosis of AML patients. Furthermore, let-7b was a potentially aberrant gene in LAMs contributed to M2-subtype characteristics, which was associated with macrophage polarization. Knockdown of let-7b in LAMs could inhibit the development of AML by repolarizing LAMs towards M1-subtype characteristics through the activation of Toll Like Receptor (TLR) and NF-κB pathway. Our study provides insight for future LAM-based immunotherapy strategies for AML.