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

被引：135

作者：

Witkowski, Matthew T. ^{[1
,2
]}

Dolgalev, Igor ^{[1
,2
,3
]}

Evensen, Nikki A. ^{[1
,2
]}

Ma, Chao ^{[7
,8
]}

Chambers, Tiffany ^{[4
]}

Roberts, Kathryn G. ^{[5
]}

Sreeram, Sheetal ^{[1
,2
]}

Dai, Yuling ^{[1
,2
]}

Tikhonova, Anastasia N. ^{[1
,2
]}

Lasry, Audrey ^{[1
,2
]}

Qu, Chunxu ^{[5
]}

Pei, Deqing ^{[5
]}

Cheng, Cheng ^{[5
]}

Robbins, Gabriel A. ^{[1
,2
]}

Pierro, Joanna ^{[1
,2
]}

Selvaraj, Shanmugapriya ^{[1
,6
]}

Mezzano, Valeria ^{[1
,6
]}

Daves, Marla ^{[4
]}

Lupo, Philip J. ^{[4
]}

Scheurer, Michael E. ^{[4
]}

Loomis, Cynthia A. ^{[1
,6
]}

Mullighan, Charles G. ^{[5
]}

Chen, Weiqiang ^{[7
,8
]}

Rabin, Karen R. ^{[4
]}

Tsirigos, Aristotelis ^{[1
,2
,3
]}

Carroll, William L. ^{[1
,2
]}

Aifantis, Iannis ^{[1
,2
]}

机构：

[1] NYU, Sch Med, Dept Pathol, New York, NY 10016 USA

[2] NYU, Laura & Isaac Perlmutter Canc Ctr, Sch Med, New York, NY 10016 USA

[3] NYU, Appl Bioinformat Labs, Sch Med, New York, NY 10016 USA

[4] Baylor Univ, Coll Med, Div Pediat Hematol Oncol, Houston, TX 77030 USA

[5] St Jude Childrens Res Hosp, Dept Pathol, 332 N Lauderdale St, Memphis, TN 38105 USA

[6] NYU, Expt Pathol Res Lab, Sch Med, New York, NY 10016 USA

[7] NYU, Dept Mech & Aerosp Engn, New York, NY 11202 USA

[8] NYU, Dept Biomed Engn, New York, NY 11202 USA

来源：

CANCER CELL | 2020年 / 37卷 / 06期

关键词：

MUTATIONS; RESISTANCE; MONOCYTES; RELAPSE; DELETION; REVEALS; TISSUE; NT5C2; P210; MICE;

D O I：

10.1016/j.ccell.2020.04.015

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

A subset of B cell acute lymphoblastic leukemia (B-ALL) patients will relapse and succumb to therapy-resis tant 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.

引用

页码：867 / +

页数：28

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