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. 2019 Apr;7(8):176.
doi: 10.21037/atm.2019.03.63.

SF3B1 mutation predicts unfavorable treatment-free survival in Chinese chronic lymphocytic leukemia patients

Yi Miao  1   2   3 , Yi-Xin Zou  1   2   3 , Dan-Ling Gu  1   2   3 , Hong-Cheng Zhu  4 , Hua-Yuan Zhu  1   2   3 , Li Wang  1   2   3 , Jin-Hua Liang  1   2   3 , Yi Xia  1   2   3 , Jia-Zhu Wu  1   2   3 , Chun-Lin Shao  5 , Lei Fan  1   2   3 , Zhen Zhang  4 , Wei Xu  1   2   3 , Jian-Yong Li  1   2   3
Affiliations

SF3B1 mutation predicts unfavorable treatment-free survival in Chinese chronic lymphocytic leukemia patients

Yi Miao et al. Ann Transl Med. 2019 Apr.

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.

Keywords: Splicing factor 3b subunit 1 mutation (SF3B1 mutation); chronic lymphocytic leukemia (CLL); prognosis; risk models.

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Conflict of interest statement

Conflicts of Interest: The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Kaplan-Meier curves of treatment-free survival (A) and overall survival (B) for different SF3B1 mutation status. SF3B1, splicing factor 3b subunit 1; UM, unmutated.
Figure 2
Figure 2
Kaplan-Meier curves of treatment-free survival for different SF3B1 mutation status stratified by age (A), IGHV mutation status (B), stage (C), TP53 status (D), and serum β2-MG concentration (E). β2-MG, β2-microglobulin; IGHV, immunoglobulin heavy variable region gene; M, mutated; SF3B1, splicing factor 3b subunit 1; TP53, tumor protein 53; UM, unmutated.
Figure 3
Figure 3
Comparison of AUC among CLL-IPI, CLL-IPI-S, and CLL-PI in 6-month TFS (A), 12-month TFS (B), and overall TFS (C). AUC, area under the curve; CI, confidence interval; CLL-IPI, chronic lymphocytic leukemia-international prognostic index; SE, standard error; SF3B1, splicing factor 3b subunit 1; TFS, treatment-free survival.
Figure 4
Figure 4
Kaplan-Meier curves of treatment-free survival stratified by four CLL-IPI (A), CLL-IPI-S (B), and CLL-PI (C) risk grades. Calibration plot of CLL-IPI (D), CLL-IPI-S (E), and CLL-PI (F). CLL-IP, chronic lymphocytic leukemia-international prognostic index.
See this image and copyright information in PMC

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