An aberrant NOTCH2-BCR signaling axis in B cells from patients with chronic GVHD

Author:

Poe Jonathan C.1ORCID,Jia Wei1,Su Hsuan1,Anand Sarah1,Rose Jeremy J.2,Tata Prasanthi V.3,Suthers Amy N.1,Jones Corbin D.4ORCID,Kuan Pei Fen5ORCID,Vincent Benjamin G.3,Serody Jonathan S.3ORCID,Horwitz Mitchell E.1ORCID,Ho Vincent T.6,Pavletic Steven Z.2ORCID,Hakim Frances T.2ORCID,Owzar Kouros7ORCID,Zhang Dadong7ORCID,Blazar Bruce R.89ORCID,Siebel Christian W.10,Chao Nelson J.1ORCID,Maillard Ivan1112ORCID,Sarantopoulos Stefanie1ORCID

Affiliation:

1. Division of Hematologic Malignancies and Cellular Therapy, Department of Medicine, Duke Cancer Institute, Duke University Medical Center, Durham, NC;

2. Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD;

3. Department of Medicine, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC;

4. Department of Biology, University of North Carolina, Chapel Hill, NC;

5. Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, NY;

6. Division of Hematologic Malignancies, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA;

7. Department of Biostatistics and Bioinformatics, Duke Cancer Institute, Duke University Medical Center, Durham, NC;

8. Division of Blood and Marrow Transplantation, Department of Pediatrics and

9. Masonic Cancer Center, University of Minnesota, Minneapolis, MN;

10. Department of Discovery Oncology, Genentech, Inc, South San Francisco, CA; and

11. Life Sciences Institute and

12. Division of Hematology-Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI

Abstract

Key Points NOTCH2 activation confers a marked increase in BCR responsiveness by cGVHD patient B cells that associates with increased BLNK. ATRA increases the IRF4-to-IRF8 ratio and blocks aberrant NOTCH2-BCR activation without affecting cGVHD patient B-cell viability/function.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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