Suppression of B-cell development genes is key to glucocorticoid efficacy in treatment of acute lymphoblastic leukemia

Author:

Kruth Karina A.12ORCID,Fang Mimi12,Shelton Dawne N.123,Abu-Halawa Ossama124,Mahling Ryan12,Yang Hongxing12,Weissman Jonathan S.56,Loh Mignon L.78ORCID,Müschen Markus78ORCID,Tasian Sarah K.910ORCID,Bassik Michael C.11,Kampmann Martin121314ORCID,Pufall Miles A.12ORCID

Affiliation:

1. Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City, IA;

2. Holden Comprehensive Cancer Center, University of Iowa Health Care, Iowa City, IA;

3. Bio-Rad Laboratories, Hercules, CA;

4. Coe College, Cedar Rapids, IA;

5. Department of Cellular and Molecular Pharmacology, University of California, San Francisco (UCSF), San Francisco, CA;

6. Howard Hughes Medical Institute, Chevy Chase, MD;

7. Department of Pediatrics, Benioff Children’s Hospital and

8. Helen Diller Family Comprehensive Cancer Center, UCSF, San Francisco, CA;

9. Division of Oncology, Center for Childhood Cancer Research, Children’s Hospital of Philadelphia, Philadelphia, PA;

10. Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA;

11. Department of Genetics, School of Medicine, Stanford University, Stanford, CA; and

12. Department of Biochemistry and Biophysics,

13. Institute for Neurodegenerative Diseases, and

14. Chan-Zuckerberg Biohub, UCSF, San Francisco, CA

Abstract

Key PointsNext-generation functional genomics identifies B-cell development genes, pathways, and feedback loops that affect dex activity in B-ALL. Suppression of lymphoid-restricted PI3Kδ synergizes with dex in B-ALL by enhancing or restoring regulation of cell-death genes.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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