TY - JOUR
T1 - Prognostic interaction between ASXL1 and TET2 mutations in chronic myelomonocytic leukemia
AU - Patnaik, M. M.
AU - Lasho, T. L.
AU - Vijayvargiya, P.
AU - Finke, C. M.
AU - Hanson, C. A.
AU - Ketterling, R. P.
AU - Gangat, N.
AU - Tefferi, A.
N1 - Funding Information:
Current study is supported in part by grants from the ‘The Henry J Predolin Foundation for Research in Leukemia, Mayo Clinic, Rochester, MN, USA’. This publication was supported by CTSA Grant Number KL2 TR000136 from the National Center for Advancing Translational Science (NCATS). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
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U2 - 10.1038/bcj.2015.113
DO - 10.1038/bcj.2015.113
M3 - Article
C2 - 26771811
AN - SCOPUS:84986253588
SN - 2044-5385
VL - 6
JO - Blood Cancer Journal
JF - Blood Cancer Journal
IS - 1
M1 - e385
ER -