Yajuan Cui1, Hongyan Tong2, Xin Du3, Bing Li1, Robert Peter Gale4, Tiejun Qin5, Jinqin Liu6, Zefeng Xu1, Yue Zhang1, Gang Huang7, Jie Jin2, Liwei Fang5, Hongli Zhang5, Lijuan Pan5, Naibo Hu5, Shiqiang Qu5, Zhijian Xiao1. 1. MDS and MPN Center, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China;; State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China. 2. Department of Hematology, The First Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou 310000, China. 3. Department of Hematology, Guangdong General Hospital, Guangzhou 510010, China. 4. Hematology Research Center, Division of Experimental Medicine, Department of Medicine, Imperial College London, London, UK. 5. MDS and MPN Center, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China. 6. State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China. 7. Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
Abstract
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.
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 CMMLpatients 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 CMMLpatients.
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