Details

Autor(en) / Beteiligte

• Patnaik, M M
• Lasho, T L
• Vijayvargiya, P
• Finke, C M
• Hanson, C A
• Ketterling, R P
• Gangat, N
• Tefferi, A

Titel

Prognostic interaction between ASXL1 and TET2 mutations in chronic myelomonocytic leukemia

Ist Teil von

• Blood cancer journal (New York), 2016-01, Vol.6 (1), p.e385-e385

Ort / Verlag

London: Nature Publishing Group UK

Erscheinungsjahr

2016

Quelle

Electronic Journals Library

Beschreibungen/Notizen

• 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.