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Extensive Remodeling of the Immune Microenvironment in B Cell Acute Lymphoblastic Leukemia.

Abstract

A subset of B cell acute lymphoblastic leukemia (B-ALL) patients will relapse and succumb to therapy-resistant disease. The bone marrow microenvironment may support B-ALL progression and treatment evasion. Utilizing single-cell approaches, we demonstrate B-ALL bone marrow immune microenvironment remodeling upon disease initiation and subsequent re-emergence during conventional chemotherapy. We uncover a role for non-classical monocytes in B-ALL survival, and demonstrate monocyte abundance at B-ALL diagnosis is predictive of pediatric and adult B-ALL patient survival. We show that human B-ALL blasts alter a vascularized microenvironment promoting monocytic differentiation, while depleting leukemia-associated monocytes in B-ALL animal models prolongs disease remission in vivo. Our profiling of the B-ALL immune microenvironment identifies extrinsic regulators of B-ALL survival supporting new immune-based therapeutic approaches for high-risk B-ALL treatment.

Authors: Witkowski MT, Dolgalev I, Evensen NA, Ma C, Chambers T, Roberts KG, Sreeram S, Dai Y, Tikhonova AN, Lasry A, Qu C, Pei D, Cheng C, Robbins GA, Pierro J, Selvaraj S, Mezzano V, Daves M, Lupo PJ, Scheurer ME, Loomis CA, Mullighan CG, Chen W, Rabin KR, Tsiri
Journal: Cancer Cell; 2020 May 14 . doi:10.1016/j.ccell.2020.04.015
Year: 2020
PubMed: PMID: 32470390 (Go to PubMed)