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An unusual, activating insertion/deletion MPL mutant in primary myelofibrosis

Leukemia volume 31, pages 1838–1839 (2017)Cite this article

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Triple-negative myeloproliferative neoplasms (TN-MPN) are defined as cases of essential thrombocythemia or primary myelofibrosis (PMF) that test negative for the principal MPN phenotype driver mutations: JAK2 V617F, CALR exon 9 frameshift mutations and MPL variants at S505 or W515.1 Recent studies have demonstrated that some cases of TN-MPN harbour non-canonical mutations in JAK2 or MPL that may be constitutional or acquired somatically.2, 3

We studied a female patient who presented at the age of 67 with pruritus, night sweats, bone pain and leucocytosis. Her peripheral blood counts were haemoglobin 12.4 g/dl, white blood cells 21.5 × 109/l and platelets 375 × 109/l with a leucoerythroblastic film. JAK2 V617F was not detected at diagnosis, and subsequent testing for MPL W515 and CALR mutations was also negative. A diagnosis of PMF with osteomyelosclerosis was made, and she was treated with localized radiotherapy for the bone pain and with photochemotherapy for the pruritis. Her disease remained stable until 2013 when she redeveloped constitutional symptoms, along with falling haemoglobin, falling platelets and an increase in circulating blasts to 3%. She was treated with ruxolitinib, followed by pacritinib and subsequently ruxolitinib again with a reduction in spleen size, but her latest assessment in 2017, 17 years after her initial diagnosis, indicated further disease progression with 10% blasts in the peripheral blood.

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Acknowledgements

This work was supported by Specialist Programme grant 13002 to NCPC from Bloodwise and to SNC from Ludwig Cancer Research, FRS-FNRS Belgium, Fondation contre le cancer project ARC10/15-027 and PAI Belgian Medical. We would like to thank Lidvine Genet for expert technical assistance.

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Authors and Affiliations

  1. Ludwig Institute for Cancer Research, Brussels Branch, Brussels, Belgium

    J-P Defour & S N Constantinescu

  2. SIGN Pole, de Duve Institute, Université Catholique de Louvain, Brussels, Belgium

    J-P Defour & S N Constantinescu

  3. Department of Clinical Biology, Cliniques Universitaires Saint-Luc, Brussels, Belgium

    J-P Defour

  4. Wessex Regional Genetics Laboratory, Salisbury NHS Foundation Trust, Salisbury, UK

    Y Hoade, A-M Reuther, A Callaway, D Ward & N C P Cross

  5. Faculty of Medicine, University of Southampton, Southampton, UK

    Y Hoade & N C P Cross

  6. Department of Haematology, Queen Elizabeth Hospital Birmingham, Birmingham, UK

    F Chen

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  1. J-P Defour
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  2. Y Hoade
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  3. A-M Reuther
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Correspondence to N C P Cross.

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Defour, JP., Hoade, Y., Reuther, AM. et al. An unusual, activating insertion/deletion MPL mutant in primary myelofibrosis. Leukemia 31, 1838–1839 (2017). https://doi.org/10.1038/leu.2017.153

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