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Hereditary thrombocythemia caused by a thrombopoietin (THPO) gain-of-function mutation associated with multiple myeloma and congenital limb defects

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Abstract

Hereditary thrombocythemia (HT) has been described as a rare benign disorder caused by mutations in the thrombopoietin (THPO) or the c-Mpl receptor genes. Here we report two families with HT resulting from a THPO c.13+1 G>C mutation in the splice donor of intron 3. In one family there were coexisting distal limb defects, whereas in the other one member developed early-onset multiple myeloma. These observations, together with previously reported patients, suggest that THPO gain of function may dysregulate the hemangioblast and disturb vasculogenesis and hematopoietic development. Overstimulation of the THPO pathway might therefore predispose to clonal hematopoietic disease and to congenital abnormalities.

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Acknowledgments

The authors would like to thank the involved families for their support and cooperation, and the Dietmar Hopp Stiftung for financial support.

Conflict of interest

The authors indicate no potential conflict of interest or competing financial interest.

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Authors and Affiliations

  1. Department of Pediatric Oncology, Hematology and Immunology, University of Heidelberg, Im Neuenheimer Feld 430, 69120, Heidelberg, Germany

    Clemens Stockklausner, Nicole Echner, Anne-Christine Klotter & Andreas E. Kulozik

  2. Department of Internal Medicine V, Hematology, Oncology and Rheumatology, University of Heidelberg, 69120, Heidelberg, Germany

    Ute Hegenbart & Peter Dreger

Authors
  1. Clemens Stockklausner
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  2. Nicole Echner
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  3. Anne-Christine Klotter
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  4. Ute Hegenbart
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  5. Peter Dreger
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  6. Andreas E. Kulozik
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Correspondence to Andreas E. Kulozik.

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Stockklausner, C., Echner, N., Klotter, AC. et al. Hereditary thrombocythemia caused by a thrombopoietin (THPO) gain-of-function mutation associated with multiple myeloma and congenital limb defects. Ann Hematol 91, 1129–1133 (2012). https://doi.org/10.1007/s00277-012-1453-y

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  • DOI: https://doi.org/10.1007/s00277-012-1453-y

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