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Colony-stimulating factor-3 receptor, watch out for polymorphisms

Leukemia volume 29, pages 1445–1446 (2015)Cite this article

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The colony-stimulating factor-3 receptor (CSF3R), also known as the receptor for granulocyte colony-stimulating factor (G-CSF), contributes to the proliferation and granulocyte differentiation of myeloid progenitor cells.1 Truncating, mostly nonsense, mutations in the cytoplasmic tail of CSF3R have been described years ago in 30–40% of patients with severe congenital neutropenia (SCN) and in around 80% of the SCN that evolve into acute myeloid leukemia (AML).2 Recently, Maxson et al.3 by employing massive deep sequencing identified activating mutations in CSF3R in chronic neutrophilic leukemia (CNL) and in atypical chronic myeloid leukemia (aCML). The incidence of activating CSF3R mutations in CNL is above 80% and controversial in aCML.3, 4 Among CNL and aCML, different frameshift and nonsense mutations truncating the cytoplasmic tail were identified, although the most prevalent was the missense T618I.3, 4 This mutation is an extracellular membrane proximal auto-activating alteration previously found in SCN/AML (named as T595I).5 The effect of T618I and of other missense mutations in malignant transformation has been proven.3 CSF3R mutations have also been found in chronic myelomonocitic leukemia, but are rare (around 4% out of 196 patients).6

Here we retrospectively screened exons 14 and 17 of CSF3R in a series of 40 patients that included 2 myelodysplastic/myeloproliferative disorders, 11 patients with leukocytosis, 17 with neutropenias, 4 with myelodysplastic syndromes, 1 with plasma cell leukemia and 5 with chronic myeloproliferative neoplasms (MPN). Among the MPNs there were two suspected cases of CNL, one associated with myeloma and other with a monoclonal gammopathy of undetermined significance (MGUS). With regard to these two cases, we previously found that they both overexpressed G-CSF by real-time PCR in sorted bone marrow CD138 cells. Thus, at that time, and before CSF3R mutations in CNL were identified, we determined that the neutrophilia of these two patients was secondary to the G-CSF production by the plasma cells according to other reported cases.7

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Authors and Affiliations

  1. Hematology Department, Hospital Universitario de Gran Canaria Doctor Negrin, Las Palmas de Gran Canaria, Spain

    C Bilbao-Sieyro, G Santana, L Torres-Miñana, C Rodriguez-Medina, M N Saez, M Perera, Angelina Lemes, S de la Iglesia, T Molero & M T Gomez-Casares

  2. Morphology Department, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain

    C Bilbao-Sieyro

  3. Medical SciencesDepartment, Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain

    T Molero

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  1. C Bilbao-Sieyro
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  2. G Santana
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Correspondence to C Bilbao-Sieyro or M T Gomez-Casares.

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Bilbao-Sieyro, C., Santana, G., Torres-Miñana, L. et al. Colony-stimulating factor-3 receptor, watch out for polymorphisms. Leukemia 29, 1445–1446 (2015). https://doi.org/10.1038/leu.2015.25

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