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Chronic Myeloproliferative Neoplasias

CSF3R T618I is a highly prevalent and specific mutation in chronic neutrophilic leukemia

Leukemia volume 27, pages 1870–1873 (2013)Cite this article

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Abstract

Truncation mutations of the receptor cytoplasmic domain for colony-stimulating factor 3 (CSF3R) are frequently seen in severe congenital neutropenia, whereas activating missense mutations affecting the extracellular domain (exon 14) have been described in hereditary neutrophilia and chronic neutrophilic leukemia (CNL). In order to clarify mutational frequency, specificity and phenotypic associations, we sequenced CSF3R exons 14–17 in 54 clinically suspected cases of CNL (n=35) or atypical chronic myeloid leukemia (aCML; n=19). Central review of these cases confirmed WHO-defined CNL in 12 patients, monoclonal gammopathy (MG)-associated CNL in 5 and WHO-defined aCML in 9. A total of 14 CSF3R mutations were detected in 13 patients, including 10 with CSF3RT618I (exon 14 mutation, sometimes annotated as CSF3R T595I). CSF3RT618I occurred exclusively in WHO-defined CNL with a mutational frequency of 83% (10 of 12 cases). CSF3R mutations were not seen in aCML or MG-associated CNL. CSF3RT618I was also absent among 170 patients with primary myelofibrosis (PMF; n=76) or chronic myelomonocytic leukemia (CMML; n=94). SETBP1 mutational frequencies in WHO-defined CNL, aCML, CMML and PMF were 33, 0, 7 and 3%, respectively. Four CSF3RT618I-mutated cases co-expressed SETBP1 mutations. We conclude that CSF3RT618I is a highly sensitive and specific molecular marker for CNL and should be incorporated into current diagnostic criteria.

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Authors and Affiliations

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

    A Pardanani, T L Lasho, R R Laborde, M Elliott & A Tefferi

  2. Division of Hematopathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA

    C A Hanson

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

    R A Knudson & R P Ketterling

  4. Division of Hematology and Medical Oncology, Oregon Health and Science University, Portland, OR, USA

    J E Maxson

  5. Knight Cancer Institute, Portland, OR, USA

    J E Maxson & J W Tyner

  6. Department of Cell and Development Biology, Oregon Health and Science University, Portland, OR, USA

    J W Tyner

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  1. A Pardanani
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  2. T L Lasho
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  4. M Elliott
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Correspondence to A Tefferi.

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Author contributions

A Pardanani and A Tefferi designed the study, contributed patient samples, analyzed the data, and wrote the paper. J Tyner contributed to data analysis and writing of the paper. MA Elliott contributed patient samples. CA Hanson reviewed bone marrow histology. RA Knudson and RP Ketterling reviewed the cytogenetics data. TL Lasho and R Laborde performed the molecular studies.

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Pardanani, A., Lasho, T., Laborde, R. et al. CSF3R T618I is a highly prevalent and specific mutation in chronic neutrophilic leukemia. Leukemia 27, 1870–1873 (2013). https://doi.org/10.1038/leu.2013.122

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