Prognostic interaction between ASXL1 and TET2 mutations in chronic myelomonocytic leukemia

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

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Abstract

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.

Original languageEnglish (US)
Article numbere385
JournalBlood Cancer Journal
Volume6
Issue number1
DOIs
StatePublished - 2016

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Leukemia, Myelomonocytic, Chronic
Mutation
Survival
Myeloid Cells
Platelet Count
Epigenomics
Monocytes

ASJC Scopus subject areas

  • Oncology
  • Hematology

Cite this

Prognostic interaction between ASXL1 and TET2 mutations in chronic myelomonocytic leukemia. / Patnaik, Mrinal M; Lasho, T. L.; Vijayvargiya, P.; Finke, C. M.; Hanson, C. A.; Ketterling, R. P.; Gangat, N.; Tefferi, Ayalew.

In: Blood Cancer Journal, Vol. 6, No. 1, e385, 2016.

Research output: Contribution to journalArticle

Patnaik, Mrinal M ; Lasho, T. L. ; Vijayvargiya, P. ; Finke, C. M. ; Hanson, C. A. ; Ketterling, R. P. ; Gangat, N. ; Tefferi, Ayalew. / Prognostic interaction between ASXL1 and TET2 mutations in chronic myelomonocytic leukemia. In: Blood Cancer Journal. 2016 ; Vol. 6, No. 1.
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abstract = "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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AU - Lasho, T. L.

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AU - Finke, C. M.

AU - Hanson, C. A.

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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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