Compound mutations in BCR-ABL1 are not major drivers of primary or secondary resistance to ponatinib in CP-CML patients

Author:

Deininger Michael W.1,Hodgson J. Graeme2,Shah Neil P.3,Cortes Jorge E.4,Kim Dong-Wook5,Nicolini Franck E.6,Talpaz Moshe7,Baccarani Michele8,Müller Martin C.9,Li Jin10,Parker Wendy T.11,Lustgarten Stephanie2,Clackson Tim2,Haluska Frank G.2,Guilhot Francois12,Kantarjian Hagop M.4,Soverini Simona13,Hochhaus Andreas14,Hughes Timothy P.1511,Rivera Victor M.2,Branford Susan1116

Affiliation:

1. Huntsman Cancer Institute University of Utah, Salt Lake City, UT;

2. ARIAD Pharmaceuticals, Inc., Cambridge, MA;

3. University of California San Francisco, San Francisco, CA;

4. Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX;

5. Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, Korea;

6. Centre Hospitalier Lyon Sud, Pierre Benite, & INSERM U1052, Lyon, France;

7. Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI;

8. Department of Hematology-Oncology “L. and A. Seragnoli,” S. Orsola-Malpighi University Hospital, Bologna, Italy;

9. III. Med. Klinik, Universitätsmedizin Mannheim, Mannheim, Germany;

10. MolecularMD, Portland, OR;

11. Department of Genetics and Molecular Pathology, SA Pathology, Centre for Cancer Biology, School of Medicine and School of Molecular and Biomedical Science, University of Adelaide, Adelaide, Australia; and

12. INSERM Clinical Investigation Center 1402, Centre Hospitalier et Universitaire de Poitiers, France;

13. Department of Experimental, Diagnostic, and Specialty Medicine, University of Bologna, Bologna, Italy;

14. Abteilung Hämatologie/Onkologie, Universitätsklinikum Jena, Jena, Germany;

15. SA Pathology and South Australian Health and Medical Research Institute, Adelaide, Australia;

16. School of Pharmacy and Medical Science, University of South Australia, Adelaide, Australia

Abstract

Key Points Ponatinib induces durable responses regardless of baseline BCR-ABL1 mutation status in CP-CML patients. No single or compound mutant consistently confers primary or secondary resistance to ponatinib in CP-CML.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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