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Molecular profiling of chronic myelomonocytic leukemia reveals diverse mutations in >80% of patients with TET2 and EZH2 being of high prognostic relevance

Leukemia volume 25, pages 877–879 (2011)Cite this article

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Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic malignancy characterized by myeloproliferative or myelodysplastic features. Factors predicting the course of disease are poorly understood and rely on clinical parameters such as anemia, splenomegaly or leukocytosis.

Recently, we characterized 81 cases according to cytogenetics and mutations in seven candidate genes, detecting an overall mutation rate of 72.8%.1 The most frequent genetic abnormalities detected using a sensitive next-generation amplicon deep-sequencing method were found in TET22 with aberrations also seen in CBL, RUNX1 and RAS.1 In this study, we aimed to further characterize this defined cohort of CMML patients by studying five additional genes: IDH1, IDH2,3, 4 NPM1, ASXL1 and EZH2.5, 6, 7 Mutations in NPM1 have been described in 6% (6/97) of CMML patients and were associated with a poor prognosis.8 ASXL1 belongs to the enhancer of trithorax and polycomb gene family and is mutated in 33% of CMML.9 Of special interest in our study was EZH2, that localizes to chromosome 7q36, proposed to function as an oncogene or a tumor suppressor gene in different diseases.5, 6, 7 EZH2 encodes the catalytic subunit of the polycomb repressive complex 2, a highly conserved histone H3 lysine 27 methyltransferase that influences stem cell renewal by epigenetic modification.6, 7 As reported by Ernst et al.6 EZH2 mutations were identified in 13% of CMML patients and myelodysplastic/myeloproliferative neoplasm patients mutated in EZH2 had been associated with an inferior outcome (P=0.0006). We aimed to identify the prevalence of mutations in CMML, identify any associations between them, as well as their correlation with morphology, cytogenetics and survival.

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References

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Authors and Affiliations

  1. MLL Munich Leukemia Laboratory, Munich, Germany

    V Grossmann, A Kohlmann, C Eder, C Haferlach, W Kern, T Haferlach & S Schnittger

  2. Human Genetics Division, School of Medicine, University of Southampton, Southampton, UK

    N C P Cross

  3. Wessex Regional Genetics Laboratory, Salisbury, UK

    N C P Cross

Authors
  1. V Grossmann
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  2. A Kohlmann
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  7. T Haferlach
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Correspondence to V Grossmann.

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Competing interests

CH, SS, WK and TH have equity ownership of MLL Munich Leukemia Laboratory. VG, AK, CE are employed by MLL Munich Leukemia Laboratory. NCPC declares no conflict of interest.

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Grossmann, V., Kohlmann, A., Eder, C. et al. Molecular profiling of chronic myelomonocytic leukemia reveals diverse mutations in >80% of patients with TET2 and EZH2 being of high prognostic relevance. Leukemia 25, 877–879 (2011). https://doi.org/10.1038/leu.2011.10

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