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Comparative Study
. 2015 Mar 10;6(7):5426-34.
doi: 10.18632/oncotarget.3101.

Frequencies of SF3B1, NOTCH1, MYD88, BIRC3 and IGHV mutations and TP53 disruptions in Chinese with chronic lymphocytic leukemia: disparities with Europeans

Yi Xia  1 , Lei Fan  1 , Li Wang  1 , Robert Peter Gale  2 , Man Wang  1 , Tian Tian  1 , Wei Wu  1 , Liang Yu  3 , Yao-Yu Chen  1 , Wei Xu  1 , Jian-Yong Li  1
Affiliations
Comparative Study

Frequencies of SF3B1, NOTCH1, MYD88, BIRC3 and IGHV mutations and TP53 disruptions in Chinese with chronic lymphocytic leukemia: disparities with Europeans

Yi Xia et al. Oncotarget. .

Abstract

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.

Keywords: MYD88; NOTCH1; SF3B1; chronic lymphocytic leukemia; mutation.

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Figures

Figure 1
Figure 1. Relationship between TP53, SF3B1, NOTCH1 and MYD88 mutations, and cytogenetic abnormalities in 307 subjects with data
Cases which presented with a cytogenetic aberration or a mutation are colored in red. Cohort1: Newly-diagnosed; cohort 2: Progressive; no therapy; cohort 3:Relapsed CLL after therapy; and cohort 4: Refractory, therapy-resistant. Subjects are highlighted in light blue, pink, light green and light purple, respectively. Brown means not analyzed.
Figure 2
Figure 2. Kaplan-Meier curves of survival (a-c) and time-to-treatment (TTT) (d-f) for SF3B1 (a and d), NOTCH1 (b and e) and MYD88 mutations (c and f)
Figure 3
Figure 3. Kaplan-Meier curves of survival (a) and TTT (b) for TP53 disruption cases with different IGHV genemutation states
Comparison of survival subjects with multiple unfavorable alterations including TP53 vs. those with TP53 only mutation is shown in (c).
See this image and copyright information in PMC

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