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Chronic Myeloproliferative Disorders

Familial essential thrombocythemia with spontaneous megakaryocyte colony formation and acquired JAK2 mutations

Leukemia volume 22, pages 1551–1556 (2008)Cite this article

Abstract

Essential thrombocythemia (ET) is a chronic myeloproliferative disorder, characterized by increased proliferation of megakaryocytes and elevated platelet count that usually occurs sporadically. We report a family with seven affected individuals in three generations, including one individual with a phenotype resembling polycythemia vera, a related disorder. Megakaryocyte (CFU-MK) colony formation occurred in the absence of added cytokines in cultures of peripheral blood from affected family members. Some reports of familial ET have identified mutations in THPO and MPL, the genes for a cytokine (thrombopoietin, TPO) that regulates platelet production and its receptor (c-MPL), respectively. In this family, the MPL gene was excluded by linkage analysis. Although TPO levels were elevated in most affected family members and evidence for linkage was found between the disease and THPO (θ=0.0, Zmax=3.0), a THPO mutation was not identified by DNA sequencing. The JAK2 V617F mutation that has been associated with 50% of sporadic cases of ET was identified as a somatic mutation, an acquired defect, in peripheral blood of the two most severely affected family members. These patients also had elevated TPO levels. Further study of familial myeloproliferative diseases will help elucidate the initiating genetic events underlying ET.

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Acknowledgements

This work was supported by the National Organization for Rare Disorders, New Fairfield, Connecticut USA and The Capital District Health Authority, Halifax, Nova Scotia, Canada.

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Authors and Affiliations

  1. Department of Pathology, Dalhousie University, Halifax, Nova Scotia, Canada

    J R Higgs, I Sadek, N K Renault & W L Greer

  2. Department of Anatomy and Neurobiology, Dalhousie University, Halifax, Nova Scotia, Canada

    P E Neumann

  3. Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada

    V W Ing

  4. Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada

    J N Berman

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  1. J R Higgs
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  7. W L Greer
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Correspondence to W L Greer.

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Higgs, J., Sadek, I., Neumann, P. et al. Familial essential thrombocythemia with spontaneous megakaryocyte colony formation and acquired JAK2 mutations. Leukemia 22, 1551–1556 (2008). https://doi.org/10.1038/leu.2008.115

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