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Chronic neutrophilic leukemia with concurrent CSF3R and SETBP1 mutations: single colony clonality studies, in vitro sensitivity to JAK inhibitors and lack of treatment response to ruxolitinib

Leukemia volume 28, pages 1363–1365 (2014)Cite this article

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Colony-stimulating factor 3 receptor gene (CSF3R) encodes the cell surface, transmembrane receptor for granulocyte colony-stimulating factor (G-CSF). Nonsense somatic mutations involving the intracytoplasmic domain of CSF3R have been described in ∼41% of patients with severe congenital neutropenia (SCN) and arise at the stem cell level.1 SCN-associated CSF3R mutations are acquired and might contribute to leukemic transformation, possibly through cooperation with other oncogenes.2, 3

A germline CSF3R transmembrane mutation (C–A substitution at nucleotide 2088; T617N) had been described in autosomal dominant hereditary neutrophilia,4 before the seminal report by Maxson et al.5 that established activating CSF3R mutations as a unique molecular marker in chronic neutrophilic leukemia (CNL). These authors subsequently reported that CSF3RT618I induced a lethal myeloproliferative disorder in a murine bone marrow transplant model.6 Treatment with ruxolitinib was reported to have a salutary effect both in this mouse model and a patient with CSF3RT618I mutation.5 Primary cells from the latter patient were reportedly sensitive to inhibition by ruxolitinib (IC50, 127 nM).

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References

  1. Germeshausen M, Welte K, Ballmaier M . In vivo expansion of cells expressing acquired CSF3R mutations in patients with severe congenital neutropenia. Blood 2009; 113: 668–670.

    Article  CAS  PubMed  Google Scholar 

  2. Kunter G, Woloszynek JR, Link DC . A truncation mutant of Csf3r cooperates with PML-RARalpha to induce acute myeloid leukemia in mice. Exp Hematol 2011; 39: 1136–1143.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Beekman R, Valkhof MG, Sanders MA, van Strien PM, Haanstra JR, Broeders L et al. Sequential gain of mutations in severe congenital neutropenia progressing to acute myeloid leukemia. Blood 2012; 119: 5071–5077.

    Article  CAS  PubMed  Google Scholar 

  4. Plo I, Zhang Y, Le Couedic JP, Nakatake M, Boulet JM, Itaya M et al. An activating mutation in the CSF3R gene induces a hereditary chronic neutrophilia. J Exp Med 2009; 206: 1701–1707.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Maxson JE, Gotlib J, Pollyea DA, Fleischman AG, Agarwal A, Eide CA et al. Oncogenic CSF3R mutations in chronic neutrophilic leukemia and atypical CML. N Engl J Med 2013; 368: 1781–1790.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Fleischman AG, Maxson JE, Luty SB, Agarwal A, Royer LR, Abel ML et al. The CSF3R T618I mutation causes a lethal neutrophilic neoplasia in mice that is responsive to therapeutic JAK inhibition. Blood 2013; 122: 3628–3631.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Kosmider O, Itzykson R, Chesnais V, Lasho T, Laborde R, Knudson R et al. Mutation of the colony-stimulating factor-3 receptor gene is a rare event with poor prognosis in chronic myelomonocytic leukemia. Leukemia 2013; 27: 1946–1949.

    Article  CAS  PubMed  Google Scholar 

  8. Pardanani A, Lasho TL, Laborde RR, Elliott M, Hanson CA, Knudson RA et al. CSF3R T618I is a highly prevalent and specific mutation in chronic neutrophilic leukemia. Leukemia 2013; 27: 1870–1873.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

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

    T L Lasho, M A Elliott, C Finke, A Pardanani & A Tefferi

  2. Division of Hematology and Oncology, Medical University of South Carolina, Charleston, SC, USA

    A Mims

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  1. T L Lasho
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  2. A Mims
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  3. M A Elliott
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  4. C Finke
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  6. A Tefferi
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Correspondence to A Tefferi.

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Lasho, T., Mims, A., Elliott, M. et al. Chronic neutrophilic leukemia with concurrent CSF3R and SETBP1 mutations: single colony clonality studies, in vitro sensitivity to JAK inhibitors and lack of treatment response to ruxolitinib. Leukemia 28, 1363–1365 (2014). https://doi.org/10.1038/leu.2014.39

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