Somatic HLA mutations expose the role of class I–mediated autoimmunity in aplastic anemia and its clonal complications

Author:

Babushok Daria V.12,Duke Jamie L.3,Xie Hongbo M.4,Stanley Natasha2,Atienza Jamie2,Perdigones Nieves2,Nicholas Peter2,Ferriola Deborah3,Li Yimei5,Huang Hugh2,Ye Wenda2,Morrissette Jennifer J. D.6,Kearns Jane6,Porter David L.1,Podsakoff Gregory M.7,Eisenlohr Laurence C.36,Biegel Jaclyn A.8910,Chou Stella T.11,Monos Dimitrios S.3,Bessler Monica12,Olson Timothy S.212

Affiliation:

1. Division of Hematology-Oncology, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA;

2. Comprehensive Bone Marrow Failure Center, Department of Pediatrics,

3. Department of Pathology and Laboratory Medicine, and

4. Department of Biomedical and Health Informatics, Children’s Hospital of Philadelphia, Philadelphia, PA;

5. Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA;

6. Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA;

7. Office of Clinical and Translational Research and

8. Division of Human Genetics, Department of Pediatrics, Children’s Hospital of Philadelphia, Philadelphia, PA;

9. Department of Pathology and Laboratory Medicine, Children’s Hospital Los Angeles, and

10. Keck School of Medicine, University of Southern California, Los Angeles, CA; and

11. Division of Hematology and

12. Division of Oncology, Department of Pediatrics, Children’s Hospital of Philadelphia, Philadelphia, PA

Abstract

Key Points Somatic HLA class I gene mutations are frequent in aAA and define HLA class I restricted autoimmunity in aAA. HLA alleles targeted by inactivating mutations are overrepresented in aAA and correlate with poor therapy response and clonal evolution.

Publisher

American Society of Hematology

Subject

Hematology

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