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

Autor:	Witkowski MT; Department of Pathology, New York University School of Medicine, New York, NY 10016, USA; Laura & Isaac Perlmutter Cancer Center, New York University School of Medicine, New York, NY 10016, USA. Electronic address: matthew.witkowski@nyulangone.org., Dolgalev I; Department of Pathology, New York University School of Medicine, New York, NY 10016, USA; Laura & Isaac Perlmutter Cancer Center, New York University School of Medicine, New York, NY 10016, USA; Applied Bioinformatics Laboratories, New York University School of Medicine, New York, NY 10016, USA., Evensen NA; Department of Pathology, New York University School of Medicine, New York, NY 10016, USA; Laura & Isaac Perlmutter Cancer Center, New York University School of Medicine, New York, NY 10016, USA., Ma C; Department of Mechanical and Aerospace Engineering, New York University, New York, NY 11202, USA; Department of Biomedical Engineering, New York University, New York, NY 11202, USA., Chambers T; Division of Pediatric Hematology/Oncology, College of Medicine, Baylor University, Houston, TX 77030, USA., Roberts KG; Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA., Sreeram S; Department of Pathology, New York University School of Medicine, New York, NY 10016, USA; Laura & Isaac Perlmutter Cancer Center, New York University School of Medicine, New York, NY 10016, USA., Dai Y; Department of Pathology, New York University School of Medicine, New York, NY 10016, USA; Laura & Isaac Perlmutter Cancer Center, New York University School of Medicine, New York, NY 10016, USA., Tikhonova AN; Department of Pathology, New York University School of Medicine, New York, NY 10016, USA; Laura & Isaac Perlmutter Cancer Center, New York University School of Medicine, New York, NY 10016, USA., Lasry A; Department of Pathology, New York University School of Medicine, New York, NY 10016, USA; Laura & Isaac Perlmutter Cancer Center, New York University School of Medicine, New York, NY 10016, USA., Qu C; Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA., Pei D; Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA., Cheng C; Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA., Robbins GA; Department of Pathology, New York University School of Medicine, New York, NY 10016, USA; Laura & Isaac Perlmutter Cancer Center, New York University School of Medicine, New York, NY 10016, USA., Pierro J; Department of Pathology, New York University School of Medicine, New York, NY 10016, USA; Laura & Isaac Perlmutter Cancer Center, New York University School of Medicine, New York, NY 10016, USA., Selvaraj S; Department of Pathology, New York University School of Medicine, New York, NY 10016, USA; Experimental Pathology Research Laboratory, New York University School of Medicine, New York, NY 10016, USA., Mezzano V; Department of Pathology, New York University School of Medicine, New York, NY 10016, USA; Experimental Pathology Research Laboratory, New York University School of Medicine, New York, NY 10016, USA., Daves M; Division of Pediatric Hematology/Oncology, College of Medicine, Baylor University, Houston, TX 77030, USA., Lupo PJ; Division of Pediatric Hematology/Oncology, College of Medicine, Baylor University, Houston, TX 77030, USA., Scheurer ME; Division of Pediatric Hematology/Oncology, College of Medicine, Baylor University, Houston, TX 77030, USA., Loomis CA; Department of Pathology, New York University School of Medicine, New York, NY 10016, USA; Experimental Pathology Research Laboratory, New York University School of Medicine, New York, NY 10016, USA., Mullighan CG; Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA., Chen W; Department of Mechanical and Aerospace Engineering, New York University, New York, NY 11202, USA; Department of Biomedical Engineering, New York University, New York, NY 11202, USA., Rabin KR; Division of Pediatric Hematology/Oncology, College of Medicine, Baylor University, Houston, TX 77030, USA., Tsirigos A; Department of Pathology, New York University School of Medicine, New York, NY 10016, USA; Laura & Isaac Perlmutter Cancer Center, New York University School of Medicine, New York, NY 10016, USA; Applied Bioinformatics Laboratories, New York University School of Medicine, New York, NY 10016, USA., Carroll WL; Department of Pathology, New York University School of Medicine, New York, NY 10016, USA; Laura & Isaac Perlmutter Cancer Center, New York University School of Medicine, New York, NY 10016, USA. Electronic address: william.carroll@nyulangone.org., Aifantis I; Department of Pathology, New York University School of Medicine, New York, NY 10016, USA; Laura & Isaac Perlmutter Cancer Center, New York University School of Medicine, New York, NY 10016, USA. Electronic address: ioannis.aifantis@nyulangone.org.
Jazyk:	angličtina
Zdroj:	Cancer cell [Cancer Cell] 2020 Jun 08; Vol. 37 (6), pp. 867-882.e12. Date of Electronic Publication: 2020 May 28.
DOI:	10.1016/j.ccell.2020.04.015
Abstrakt:	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. Competing Interests: Declaration of Interests The authors declare no competing interests. (Copyright © 2020 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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