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Comparison of Frequency and Sensitivity of BCR-ABL1 Kinase Domain Mutations in Asian and White Patients With Imatinib-resistant Chronic-Phase Chronic Myeloid Leukemia.
- Source :
-
Clinical lymphoma, myeloma & leukemia [Clin Lymphoma Myeloma Leuk] 2018 Oct; Vol. 18 (10), pp. e391-e399. Date of Electronic Publication: 2018 Jul 04. - Publication Year :
- 2018
-
Abstract
- Introduction: BCR-ABL1 mutations require consideration during second-line tyrosine kinase inhibitor selection for patients with chronic myeloid leukemia (CML). The present retrospective analysis compared the frequency of BCR-ABL1 mutations in Asian and white patients in whom imatinib therapy had failed.<br />Patients and Methods: A nonstudy cohort (76 Asian patients from community clinical practices) and 2 study cohorts (29 Asian and 352 white patients from dasatinib phase II and III clinical trials) were identified.<br />Results: In the nonstudy cohort, 80 mutations were identified; the most frequent was T315I (15%), followed by phosphate-binding loop mutations E255K (11%), G250E (10%), and Y253H (10%). Asian patients had a greater proportion of T315I and phosphate-binding loop mutations compared with the white patients. The nonstudy cohort was less likely to have multiple mutations compared with either study cohort. Single mutations highly resistant to dasatinib, nilotinib, and bosutinib were more frequent in the Asian than in the white cohorts.<br />Conclusion: These results suggest that mutational analysis findings will be invaluable for choosing an appropriate second-line tyrosine kinase inhibitor in Asia.<br /> (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Adolescent
Adult
Aged
Aged, 80 and over
Aniline Compounds administration & dosage
Biomarkers, Tumor
Clinical Trials, Phase II as Topic
Clinical Trials, Phase III as Topic
Cohort Studies
DNA Mutational Analysis
Dasatinib administration & dosage
Female
Follow-Up Studies
Gene Frequency
Humans
Imatinib Mesylate administration & dosage
Leukemia, Myeloid, Chronic-Phase drug therapy
Male
Middle Aged
Nitriles administration & dosage
Prognosis
Pyrimidines administration & dosage
Quinolines administration & dosage
Survival Rate
Young Adult
Antineoplastic Combined Chemotherapy Protocols therapeutic use
Asian People genetics
Drug Resistance, Neoplasm genetics
Fusion Proteins, bcr-abl genetics
Leukemia, Myeloid, Chronic-Phase ethnology
Leukemia, Myeloid, Chronic-Phase genetics
Mutation
White People genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2152-2669
- Volume :
- 18
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Clinical lymphoma, myeloma & leukemia
- Publication Type :
- Academic Journal
- Accession number :
- 30082224
- Full Text :
- https://doi.org/10.1016/j.clml.2018.06.031