ASXL1 and SETBP1 mutations and their prognostic contribution in chronic myelomonocytic leukemia: A two-center study of 466 patients

M. M. Patnaik, R. Itzykson, T. L. Lasho, O. Kosmider, C. M. Finke, C. A. Hanson, R. A. Knudson, R. P. Ketterling, A. Tefferi, E. Solary

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135 Scopus citations

Abstract

In a cohort of 466 patients, we sought to clarify the prognostic relevance of ASXL1 and SETBP1 mutations, among others, in World Health Organization-defined chronic myelomonocytic leukemia (CMML) and its added value to the Mayo prognostic model. In univariate analysis, survival was adversely affected by ASXL1 (nonsense and frameshift) but not SETBP1 mutations. In multivariable analysis, ASXL1 mutations, absolute monocyte count >10×10(9)/l, hemoglobin <10 g/dl, platelets <100×10(9)/l and circulating immature myeloid cells were independently predictive of shortened survival: hazard ratio (95% confidence interval (CI)) values were 1.5 (1.1-2.0), 2.2 (1.6-3.1), 2.0 (1.6-2.6), 1.5 (1.2-1.9) and 2.0 (1.4-2.7), respectively. A regression coefficient-based prognostic model based on these five risk factors delineated high (>3 risk factors; HR 6.2, 95% CI 3.7-10.4) intermediate-2 (2 risk factors; HR 3.4, 95% CI 2.0-5.6) intermediate-1 (one risk factor; HR 1.9, 95% CI 1.1-3.3) and low (no risk factors) risk categories with median survivals of 16, 31, 59 and 97 months, respectively. Neither ASXL1 nor SETBP1 mutations predicted leukemic transformation. The current study confirms the independent prognostic value of nonsense/frameshift ASXL1 mutations in CMML and signifies its added value to the Mayo prognostic model, as had been shown previously in the French consortium model.

Original languageEnglish (US)
Pages (from-to)2206-2212
Number of pages7
JournalLeukemia
Volume28
Issue number11
DOIs
StatePublished - Nov 1 2014

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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    Patnaik, M. M., Itzykson, R., Lasho, T. L., Kosmider, O., Finke, C. M., Hanson, C. A., Knudson, R. A., Ketterling, R. P., Tefferi, A., & Solary, E. (2014). ASXL1 and SETBP1 mutations and their prognostic contribution in chronic myelomonocytic leukemia: A two-center study of 466 patients. Leukemia, 28(11), 2206-2212. https://doi.org/10.1038/leu.2014.125