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Mutation of the colony-stimulating factor-3 receptor gene is a rare event with poor prognosis in chronic myelomonocytic leukemia

Leukemia volume 27, pages 1946–1949 (2013)Cite this article

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Occasionally, a CSF3R mutation that affects the extracellular domain of the receptor, that is, CSF3R T618I (Figure 1, using ENST00000373103 for numbering and C-to-T substitution at nucleotide 1853, exon 14, initially described as T595I), has been detected in transformed SCN5 and de novo AML.6 Interestingly, this mutation confers autonomous signaling properties to the receptor,6 recapitulating the consequences of a germ-line T640N CSF3R mutation (Figure 1, C-to-A substitution at nucleotide 2088; exon 16, initially described as T617N). This latter mutation was identified in a family with autosomal dominant hereditary neutrophilia, enhanced circulating CD34-positive myeloid progenitors and splenomegaly.7

Very recently, acquired CSF3R mutations, in most cases T618I, were identified in a majority of patients with chronic neutrophilic leukemia (CNL).8, 9 Here, we show that CSF3R somatic mutations can be identified in ∼4% of the patients with chronic myelomonocytic leukemia (CMML). These mutations, which affect distinct residues in CSF3R as compared with SCN, CNL and AML patients, are frequently associated with mutations in ASXL1 gene and have a poor prognostic impact on overall (OS) and AML-free survival in univariate analysis.

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Acknowledgements

This study was supported by grants from the Program Hospitalier de Recherche Clinique (MYELOMONO to ES), the Association Laurette Fugain (to ND), the Ligue Nationale Contre le Cancer (to ES), and translational research grants from the French National Cancer Institute INCa (to MF, and to ES).

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Authors and Affiliations

  1. Institut Cochin, Paris, France

    O Kosmider, V Chesnais, A Gauthier & M Fontenay

  2. Université Paris Descartes, Paris, France

    O Kosmider, V Chesnais, A Gauthier & M Fontenay

  3. Assistance Publique-Hôpitaux de Paris, Hôpital Cochin, Paris, France

    O Kosmider, V Chesnais, A Gauthier & M Fontenay

  4. Institut Gustave Roussy, Villejuif, France

    R Itzykson, J Merlevede, M Morabito, N Droin & E Solary

  5. INSERM U1009, Villejuif, France

    R Itzykson, J Merlevede, M Morabito, N Droin & E Solary

  6. Université Paris-Sud 11, Orsay, France

    R Itzykson, J Merlevede, M Morabito, N Droin & E Solary

  7. Division of Hematology, Department of Medicine, Mayo Clinic Rochester, Rochester, MN, USA

    T Lasho, R Laborde & A Tefferi

  8. Division of Cytogenetics, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA

    R Knudson

  9. Assistance Publique-Hôpitaux de Paris, Hôpital Avicenne, Bobigny, France

    L Ades

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  1. O Kosmider
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Correspondence to E Solary.

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Kosmider, O., Itzykson, R., Chesnais, V. et al. Mutation of the colony-stimulating factor-3 receptor gene is a rare event with poor prognosis in chronic myelomonocytic leukemia. Leukemia 27, 1946–1949 (2013). https://doi.org/10.1038/leu.2013.182

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