期刊
ONCOTARGET
卷 6, 期 7, 页码 5426-5434出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.3101
关键词
SF3B1; NOTCH1; MYD88; mutation; chronic lymphocytic leukemia
资金
- National Natural Science Foundation of China [30871104, 30971296, 81000216, 81100352, 81170485, 81170486, 81170488, 81200360, 81300408, 81370657]
- Natural Science Foundation of Jiangsu Province [BK2012484, BK20141028]
- Health Department of Jiangsu Province [K201108]
- Jiangsu Province's Medical Elite Program [RC2011169]
- National Public Health Grand Research Foundation [201202017]
- Program for Development of Innovative Research Teams in the First Affiliated Hospital of Nanjing Medical University
- Project of National Key Clinical Specialty
- National Science & Technology Pillar Program [2014BAI09B12]
- Jiangsu Provincial Special Program of Medical Science [BL2014086]
- NIHR Biomedical Research Centre
We studied 307 consecutive Chinese with chronic lymphocytic leukemia (CLL) in diverse disease-stages before and after diverse therapies for mutations in several CLL-related genes. Mutation frequencies were SF3B1, 5%, NOTCH1, 8%, MYD88, 8%, BIRC3, 2%, TP53, 15% and IGHV, 60%. Several of these frequencies differ from those reported in persons of predominately European descent with CLL. Biological and clinical associations were detected including SF3B1 and NOTCH1 mutations with un-mutated IGHV, MYD88 mutations with mutated IGHV, SF3B1 mutations with fludarabine-resistant CLL and NOTCH1 mutation with advanced Binet disease stage and with +12. The NOTCH1 correlation with briefer survival was confirmed in multivariate analyses but the SF3B1 correlation was confounded by concurrent mutations in TP53 and germline IGHV. We show differences in incidence and prognostic impact of mutations in Chinese and CLL compared with persons of predominately European descent with CLL. These data may give insights into the etiology and biology of CLL and suggests different risk stratification models may be needed for different CLL populations.
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