Yi Miao1,2,3, Yi-Xin Zou1,2,3, Dan-Ling Gu1,2,3, Hong-Cheng Zhu4, Hua-Yuan Zhu1,2,3, Li Wang1,2,3, Jin-Hua Liang1,2,3, Yi Xia1,2,3, Jia-Zhu Wu1,2,3, Chun-Lin Shao5, Lei Fan1,2,3, Zhen Zhang4, Wei Xu1,2,3, Jian-Yong Li1,2,3. 1. Department of Hematology, the First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing 210029, China. 2. Key Laboratory of Hematology of Nanjing Medical University, Nanjing 210029, China. 3. Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing 210029, China. 4. Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China. 5. Institute of Radiation Medicine, Fudan University, Shanghai 200032, China.
Abstract
BACKGROUND: Splicing factor 3b subunit 1 (SF3B1), a splicing factor modulating RNA alternative splicing, is frequently mutated in multiple hematological malignancies including myelodysplastic syndromes and chronic lymphocytic leukemia (CLL). The clinical impact of SF3B1 mutation on CLL remains controversial especially for patients of Asian descent. METHODS: We retrospectively analyzed the frequency of SF3B1 mutation by Sanger sequencing in 399 newly diagnosed Chinese CLL patients. RESULTS: SF3B1 mutation was detected in 5.5% (22/399) of the studied cohort with 59.1% of them being c.A2098G (p.K700E). SF3B1 mutation was common in patients with unmutated immunoglobulin heavy chain variable region gene, positive CD38 and positive ZAP-70. Survival analysis showed that SF3B1 mutation was associated with short treatment-free survival (TFS), but not overall survival (OS). We then developed 2 new risk models, named CLL-IPI-S and CLL-PI, according to the SF3B1 mutation status and CLL-international prognostic index (CLL-IPI); CLL-PI showed greater power to predict TFS than CLL-IPI in Chinese CLL patients. CONCLUSIONS: Our data suggest a low incidence and adverse clinical significance of SF3B1 mutation in newly diagnosed Chinese CLL patients.
BACKGROUND: Splicing factor 3b subunit 1 (SF3B1), a splicing factor modulating RNA alternative splicing, is frequently mutated in multiple hematological malignancies including myelodysplastic syndromes and chronic lymphocytic leukemia (CLL). The clinical impact of SF3B1 mutation on CLL remains controversial especially for patients of Asian descent. METHODS: We retrospectively analyzed the frequency of SF3B1 mutation by Sanger sequencing in 399 newly diagnosed Chinese CLL patients. RESULTS: SF3B1 mutation was detected in 5.5% (22/399) of the studied cohort with 59.1% of them being c.A2098G (p.K700E). SF3B1 mutation was common in patients with unmutated immunoglobulin heavy chain variable region gene, positive CD38 and positive ZAP-70. Survival analysis showed that SF3B1 mutation was associated with short treatment-free survival (TFS), but not overall survival (OS). We then developed 2 new risk models, named CLL-IPI-S and CLL-PI, according to the SF3B1 mutation status and CLL-international prognostic index (CLL-IPI); CLL-PI showed greater power to predict TFS than CLL-IPI in Chinese CLL patients. CONCLUSIONS: Our data suggest a low incidence and adverse clinical significance of SF3B1 mutation in newly diagnosed Chinese CLL patients.
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