Targeted Rho-associated kinase 2 inhibition suppresses murine and human chronic GVHD through a Stat3-dependent mechanism

Author:

Flynn Ryan1,Paz Katelyn1,Du Jing1,Reichenbach Dawn K.1,Taylor Patricia A.1,Panoskaltsis-Mortari Angela1,Vulic Ante2,Luznik Leo2,MacDonald Kelli K. P.3,Hill Geoffrey R.3,Nyuydzefe Melanie S.4,Weiss Jonathan M.4,Chen Wei4,Trzeciak Alissa4,Serody Jon S.5,Aguilar Ethan G.6,Murphy William J.6,Maillard Ivan7,Munn David8,Koreth John9,Cutler Corey S.9,Antin Joseph H.9,Ritz Jerome9,Waksal Samuel D.4,Zanin-Zhorov Alexandra4,Blazar Bruce R.1

Affiliation:

1. Division of Blood and Marrow Transplantation, Masonic Cancer Center and Department of Pediatrics, University of Minnesota, Minneapolis, MN;

2. Sidney Kimmel Comprehensive Cancer Center and Department of Oncology, The Johns Hopkins University, Baltimore, MD;

3. Department of Immunology, Queensland Institute of Medical Research, Brisbane, Australia;

4. Kadmon Research Institute, New York, NY;

5. Lineberger Comprehensive Cancer Center Division of Hematology/Oncology, Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC;

6. Department of Dermatology, School of Medicine, University of California, Davis, Sacramento, CA;

7. Life Sciences Institute and Division of Hematology-Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI;

8. Department of Pediatrics, Georgia Health Sciences University, Augusta, GA; and

9. Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA

Abstract

Key Points The ROCK2 inhibitor, KD025, decreases chronic GVHD pathology in multiple murine models. KD025 inhibits STAT3 phosphorylation to decrease RORγt and Bcl6 expression in both murine and human cells.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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