TET2 mutations were predictive of inferior prognosis in the presence of ASXL1 mutations in patients with chronic myelomonocytic leukemia

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.