| Literature DB >> 32470390 |
Matthew T Witkowski1, Igor Dolgalev2, Nikki A Evensen3, Chao Ma4, Tiffany Chambers5, Kathryn G Roberts6, Sheetal Sreeram3, Yuling Dai3, Anastasia N Tikhonova3, Audrey Lasry3, Chunxu Qu6, Deqing Pei6, Cheng Cheng6, Gabriel A Robbins3, Joanna Pierro3, Shanmugapriya Selvaraj7, Valeria Mezzano7, Marla Daves5, Philip J Lupo5, Michael E Scheurer5, Cynthia A Loomis7, Charles G Mullighan6, Weiqiang Chen4, Karen R Rabin5, Aristotelis Tsirigos2, William L Carroll8, Iannis Aifantis9.
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.Entities:
Keywords: acute lymphoblastic leukemia; chemotherapy; immune microenvironment; monocytes; relapse; single cell
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Year: 2020 PMID： 32470390 PMCID： PMC7341535 DOI： 10.1016/j.ccell.2020.04.015
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743