MAPK signaling cascades mediate distinct glucocorticoid resistance mechanisms in pediatric leukemia

Author:

Jones Courtney L.1,Gearheart Christy M.2,Fosmire Susan2,Delgado-Martin Cristina3,Evensen Nikki A.1,Bride Karen4,Waanders Angela J.4,Pais Faye3,Wang Jinhua15,Bhatla Teena1,Bitterman Danielle S.1,de Rijk Simone R.1,Bourgeois Wallace1,Dandekar Smita1,Park Eugene6,Burleson Tamara M.2,Madhusoodhan Pillai Pallavi1,Teachey David T.4,Raetz Elizabeth A.7,Hermiston Michelle L.3,Müschen Markus6,Loh Mignon L.3,Hunger Stephen P.4,Zhang Jinghui8,Garabedian Michael J.9,Porter Christopher C.2,Carroll William L.1

Affiliation:

1. Laura and Isaac Perlmutter Cancer Center, New York University Langone Medical Center, New York, NY;

2. Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO;

3. Department of Pediatrics, University of California School of Medicine, San Francisco, CA;

4. Department of Pediatrics, Children’s Hospital of Philadelphia, Philadelphia, PA;

5. Center for Health Informatics and Bioinformatics, New York University Langone Medical Center, New York, NY;

6. Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA;

7. Division of Pediatric Hematology and Oncology, University of Utah, Salt Lake City, UT;

8. Department of Computational Biology, St Jude Children’s Research Hospital, Memphis, TN; and

9. Department of Microbiology, New York University Langone Medical Center, New York, NY

Abstract

Key Points Genetic or pharmacologic inhibition of MEK4 and MEK2 enhances prednisolone-induced cell death in ALL models. MAPK signaling cascades are activated at relapse compared to diagnosis in ALL samples and have enhanced response to MEK inhibition.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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