Original Article

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

  • Leukemia volume 28, pages 22062212 (2014)
  • doi:10.1038/leu.2014.125
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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.

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Acknowledgements

This study is supported in part by grants from the ‘Myeloproliferative Disorders Foundation, Chicago, IL, USA’ and ‘The Henry J. Predolin Foundation for Research in Leukemia, Mayo Clinic, Rochester, MN, USA’.

Author information

Affiliations

  1. Division of Hematology, Mayo Clinic, Rochester, MN, USA

    • M M Patnaik
    • , T L Lasho
    • , C M Finke
    •  & A Tefferi
  2. Université Paris Descartes, Paris, France

    • R Itzykson
    •  & O Kosmider
  3. Institut Gustave Roussy, Villejuif, France

    • R Itzykson
    •  & E Solary
  4. Université Paris-Sud 11, Orsay, France

    • R Itzykson
    •  & E Solary
  5. Institut Cochin, Paris, France

    • O Kosmider
  6. Division of Hematopathology, Mayo Clinic, Rochester, MN, USA

    • C A Hanson
  7. Division of Cytogenetics, Mayo Clinic, Rochester, MN, USA

    • R A Knudson
    •  & R P Ketterling
  8. INSERM U1009, Villejuif, France

    • E Solary

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Competing interests

The authors declare no conflict of interest.

Corresponding authors

Correspondence to A Tefferi or E Solary.

Supplementary information

Word documents

  1. 1.

    Supplementary Table

Supplementary Information accompanies this paper on the Leukemia website (http://www.nature.com/leu)