期刊
CANCER CELL
卷 37, 期 6, 页码 867-+出版社
CELL PRESS
DOI: 10.1016/j.ccell.2020.04.015
关键词
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资金
- Cancer Center Support Grant at the Laura and Isaac Perlmutter Cancer Center [P30CA016087]
- Experimental Pathology Research Lab by the Cancer Center Support Grant [P30CA016087]
- PerkinElmer Vectra multispectral imaging system [S10 OD021747]
- US NIH [RO1CA202025, RO1CA202027, RO1CA216421, 1RO1CA228135, PO1CA229086]
- Leukemia & Lymphoma Society (TRP) [6580]
- Alex's Lemonade Stand Foundation for Childhood Cancer
- St. Baldrick's Cancer Research Foundation
- Jeffrey Pride Foundation for Pediatric Cancer Research
- Children's Oncology Group Foundation
- New York State Department of Health (NYSTEM Program)
- Leukemia and Lymphoma Society
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.
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