Signalling thresholds and negative B-cell selection in acute lymphoblastic leukaemia

Zhengshan Chen, Seyedmehdi Shojaee, Maike Buchner, Huimin Geng, Jae Woong Lee, Lars Klemm, Björn Titz, Thomas G. Graeber, Eugene Park, Ying Xim Tan, Anne Satterthwaite, Elisabeth Paietta, Stephen P. Hunger, Cheryl L. Willman, Ari Melnick, Mignon L. Loh, Jae U. Jung, John E. Coligan, Silvia Bolland, Tak W. Mak, Andre Limnander, Hassan Jumaa, Michael Reth, Arthur Weiss, Clifford A. Lowell and Markus Müschen ()
Additional contact information
Zhengshan Chen: University of California
Seyedmehdi Shojaee: University of California
Maike Buchner: University of California
Huimin Geng: University of California
Jae Woong Lee: University of California
Lars Klemm: University of California
Björn Titz: Crump Institute for Molecular Imaging, University of California
Thomas G. Graeber: Crump Institute for Molecular Imaging, University of California
Eugene Park: University of California
Ying Xim Tan: Rosalind Russell-Ephraim P. Engleman Medical Research Center for Arthritis, Howard Hughes Medical Institute, University of California
Anne Satterthwaite: University of Texas Southwestern Medical Center
Elisabeth Paietta: Albert Einstein College of Medicine
Stephen P. Hunger: Children’s Hospital of Philadelphia
Cheryl L. Willman: University of New Mexico Cancer Center
Ari Melnick: Weill Cornell Medical College
Mignon L. Loh: Pediatric Hematology-Oncology, University of California
Jae U. Jung: University of Southern California
John E. Coligan: Receptor Cell Biology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Silvia Bolland: Autoimmunity and Functional Genomics Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Tak W. Mak: The Campbell Family Institute for Breast Cancer Research, University Health Network, 620 University Avenue, Toronto, Ontario M5G 2M9, Canada
Andre Limnander: University of California
Hassan Jumaa: Institute of Immunology, University Clinics Ulm, 89081 Ulm, Germany
Michael Reth: BIOSS Centre for Biological Signalling Studies and Faculty of Biology, Albert-Ludwigs-Universität Freiburg, and MPI of Immunbiologie and Epigenetics, 79104 Freiburg, Germany
Arthur Weiss: Rosalind Russell-Ephraim P. Engleman Medical Research Center for Arthritis, Howard Hughes Medical Institute, University of California
Clifford A. Lowell: University of California
Markus Müschen: University of California

Nature, 2015, vol. 521, issue 7552, 357-361

Abstract: This study shows that, despite malignant transformation, autoimmune checkpoints are still functional in B-cell leukaemia, with targeted activation of these checkpoints effectively killing patient-derived B-cell leukaemia in a transplant model; the results represent a novel strategy to overcome drug resistance in leukaemia patients.

Date: 2015
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DOI: 10.1038/nature14231

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