Prognostic interaction between ASXL1 and TET2 mutations in chronic myelomonocytic leukemia

• Published in: Blood cancer journal (New York) 2016-01, Vol.6 (1), p.e385-e385
• Main Authors: Patnaik, M M, Lasho, T L, Vijayvargiya, P, Finke, C M, Hanson, C A, Ketterling, R P, Gangat, N, Tefferi, A
• Format: Article
• Language: English
• Subjects: 45; 45/23; 631/208; 631/67; Adolescent; Adult; Aged; Aged, 80 and over; Biomedical and Life Sciences; Biomedicine; Cancer Research; Dioxygenases; DNA-Binding Proteins - genetics; Epistasis, Genetic; Female; Gene Expression Regulation, Leukemic; Gene Frequency; Genetic Association Studies; Hematology; Humans; Leukemia, Myelomonocytic, Chronic - genetics; Leukemia, Myelomonocytic, Chronic - mortality; Male; Middle Aged; Mutation; Oncology; Original; original-article; Prognosis; Proto-Oncogene Proteins - genetics; Repressor Proteins - genetics; Young Adult
• ISSN: 2044-5385; 2044-5385
• DOI: 10.1038/bcj.2015.113

Mutations involving epigenetic regulators ( TET2 ~60% and ASXL1 ~40%) and splicing components ( SRSF2 ~50%) are frequent in chronic myelomonocytic leukemia (CMML). On a 27-gene targeted capture panel performed on 175 CMML patients (66% males, median age 70 years), common mutations included: TET2 46%, ASXL1 47%, SRSF2 45% and SETBP1 19%. A total of 172 (98%) patients had at least one mutation, 21 (12%) had 2, 24 (14%) had 3 and 30 (17%) had >3 mutations. In a univariate analysis, the presence of ASXL1 mutations ( P =0.02) and the absence of TET2 mutations ( P =0.03), adversely impacted survival; while the number of concurrent mutations had no impact ( P =0.3). In a multivariable analysis that included hemoglobin, platelet count, absolute monocyte count and circulating immature myeloid cells (Mayo model), the presence of ASXL1 mutations ( P =0.01) and absence of TET2 mutations ( P =0.003) retained prognostic significance. Patients were stratified into four categories: ASXL1wt/TET2wt ( n =56), ASXL1mut/TET2wt ( n =31), ASXL1mut/TET2mut ( n =50) and ASXL1wt/TET2mut ( n =38). Survival data demonstrated a significant difference in favor of ASXL1wt/TET2mut (38 months; P =0.016), compared with those with ASXL1wt/TET2wt (19 months), ASXL1mut/TET2wt (21 months) and ASXL1mut/TET2mut (16 months) ( P =0.3). We confirm the negative prognostic impact imparted by ASXL1 mutations and suggest a favorable impact from TET2 mutations in the absence of ASXL1 mutations.