TY - JOUR
T1 - TET2 mutations were predictive of inferior prognosis in the presence of ASXL1 mutations in patients with chronic myelomonocytic leukemia
AU - Cui, Yajuan
AU - Tong, Hongyan
AU - Du, Xin
AU - Li, Bing
AU - Gale, Robert Peter
AU - Qin, Tiejun
AU - Liu, Jinqin
AU - Xu, Zefeng
AU - Zhang, Yue
AU - Huang, Gang
AU - Jin, Jie
AU - Fang, Liwei
AU - Zhang, Hongli
AU - Pan, Lijuan
AU - Hu, Naibo
AU - Qu, Shiqiang
AU - Xiao, Zhijian
N1 - Publisher Copyright:
© Stem Cell Investigation. All rights reserved.
PY - 2016/9/1
Y1 - 2016/9/1
N2 - Background: Somatic mutations involving epigenetic regulators, histone modification and chromatin regulation, splicing components, transcription factors and signaling regulator genes are common in chronic myelomonocytic leukemia (CMML) patients. It has been consensus that ASXL1 mutations have adversely impact on overall survival (OS), while the effect of TET2 mutations remains controversial and undefined. Methods: ASXL1 and TET2 mutations were analyzed in 141 patients with CMML using Sanger sequencing, with the aim to identify the interplay of ASXL1 and TET2 mutations in the prognosis of CMML. Results: Sixty-five (46.1%) of the CMML patients harbored ASXL1 mutations (frameshift and nonsense), and 46 (32.6%) had TET2 mutations (frame shift, nonsense and missense). In a separate multivariable analysis that included the Mayo Prognostic Model as a single variable along with ASXL1wt/TET2wt, the respective hazard ratios of ASXL1mut/TET2mut, ASXL1mut/TET2wt and ASXL1wt/TET2mut were 4.7 (95% CI, 2.2-10.3; P<0.001), 2.2 (95% CI, 1.1-4.2; P=0.025) and 1.3 (95% CI, 0.6-2.5; P=0.521). Conclusions: Our study showed that ASXL1 mutations predict inferior OS, and additional TET2 mutations were associated with poor survival in the presence of ASXL1 mutations of CMML patients.
AB - Background: Somatic mutations involving epigenetic regulators, histone modification and chromatin regulation, splicing components, transcription factors and signaling regulator genes are common in chronic myelomonocytic leukemia (CMML) patients. It has been consensus that ASXL1 mutations have adversely impact on overall survival (OS), while the effect of TET2 mutations remains controversial and undefined. Methods: ASXL1 and TET2 mutations were analyzed in 141 patients with CMML using Sanger sequencing, with the aim to identify the interplay of ASXL1 and TET2 mutations in the prognosis of CMML. Results: Sixty-five (46.1%) of the CMML patients harbored ASXL1 mutations (frameshift and nonsense), and 46 (32.6%) had TET2 mutations (frame shift, nonsense and missense). In a separate multivariable analysis that included the Mayo Prognostic Model as a single variable along with ASXL1wt/TET2wt, the respective hazard ratios of ASXL1mut/TET2mut, ASXL1mut/TET2wt and ASXL1wt/TET2mut were 4.7 (95% CI, 2.2-10.3; P<0.001), 2.2 (95% CI, 1.1-4.2; P=0.025) and 1.3 (95% CI, 0.6-2.5; P=0.521). Conclusions: Our study showed that ASXL1 mutations predict inferior OS, and additional TET2 mutations were associated with poor survival in the presence of ASXL1 mutations of CMML patients.
KW - ASXL1 mutations
KW - Chronic myelomonocytic leukemia (CMML)
KW - Prognosis
KW - TET2 mutations
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U2 - 10.21037/sci.2016.09.04
DO - 10.21037/sci.2016.09.04
M3 - Article
C2 - 27777939
AN - SCOPUS:84995395275
SN - 2306-9759
VL - 2016
JO - Stem Cell Investigation
JF - Stem Cell Investigation
IS - SEP
M1 - 50
ER -