Ruxolitinib-induced defects in DNA repair cause sensitivity to PARP inhibitors in myeloproliferative neoplasms

Author:

Nieborowska-Skorska Margaret1,Maifrede Silvia1,Dasgupta Yashodhara1,Sullivan Katherine1,Flis Sylwia12,Le Bac Viet13,Solecka Martyna1,Belyaeva Elizaveta A.4,Kubovcakova Lucia5,Nawrocki Morgan1,Kirschner Martin6,Zhao Huaqing7,Prchal Josef T.8,Piwocka Katarzyna3,Moliterno Alison R.9,Wasik Mariusz4,Koschmieder Steffen6,Green Tony R.101112,Skoda Radek C.5,Skorski Tomasz113

Affiliation:

1. Department of Microbiology and Immunology, Lewis Katz School of Medicine, Temple University, Philadelphia, PA;

2. Department of Pharmacology, National Medicines Institute, Warsaw, Poland;

3. Laboratory of Cytometry, Nencki Institute of Experimental Biology, Warsaw, Poland;

4. Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA;

5. Department of Biomedicine, University Hospital Basel/University of Basel, Basel, Switzerland;

6. Department of Hematology, Oncology, Hemostaseology and Stem Cell Transplantation, Faculty of Medicine, Rheinisch-Westfälische Technische Hochschule Aachen University, Aachen, Germany;

7. Department of Clinical Sciences, Lewis Katz School of Medicine, Temple University, Philadelphia, PA;

8. School of Medicine, University of Utah, Salt Lake City, UT;

9. Division of Hematology, Department of Medicine, School of Medicine, The Johns Hopkins University, Baltimore, MD; and

10. Cambridge Institute for Medical Research,

11. Wellcome–Medical Research Council Cambridge Stem Cell Institute, and

12. Department of Haematology, University of Cambridge, Cambridge, United Kingdom; and

13. Fels Institute for Cancer Research and Molecular Biology, Lewis Katz School of Medicine, Temple University, Philadelphia, PA

Abstract

Key Points Ruxolitinib caused DNA repair defects and sensitized MPN stem and progenitor cells to PARP inhibitors. Quiescent and proliferating MPN cells were eliminated by ruxolitinib and olaparib plus or minus hydroxyurea.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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