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.

journal_name

Cancer Cell

journal_title

Cancer cell

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,

doi

10.1016/j.ccell.2020.04.015

subject

Has Abstract

pub_date

2020-06-08 00:00:00

pages

867-882.e12

issue

6

eissn

1535-6108

issn

1878-3686

pii

S1535-6108(20)30214-2

journal_volume

37

pub_type

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