The Ph-positive and Ph-negative myeloproliferative neoplasms: Some topical pre-clinical and clinical issues

Richard A. van Etten, Steffen Koschmieder, Francois Delhommeau, Danilo Perrotti, Tessa Holyoake, Animesh Pardanani, Ruben Mesa, Tony Green, Amr R. Ibrahim, Tariq Mughal, Robert Peter Gale, John Goldman

Research output: Contribution to journalReview article

15 Scopus citations

Abstract

This review focuses on topical issues in the biology and treatment of the myeloproliferative neoplasms (MPNs). Studies in transgenic mice suggest that BCR-ABL1 reduces the fraction of self-renewing 'leukemic' stem cells in the bone marrow but that some of these cells survive treatment with imatinib. This also seems to operate in humans. Data from models also strongly support the notion that JAK2V617F can initiate and sustain MPNs in mice; relevance to disease in humans is less clear. These data also support the hypothesis that level of JAK2V617F expression influences the MPN phenotype: higher levels favor erythrocytosis whereas lower levels favor thrombocytosis. Although TET2-mutations were thought to precede JAK2V617F in some persons with MPNs, it now appears that TET2 mutations may occur after JAK2V617F. Further understanding of sig-nal-transduction pathways activated in chronic myeloid leukemia suggests various possible targets for new therapies including the WNT/beta catenin, notch and hedgehog pathways. Finally, the clinical role of the new JAK2- and BCR-ABL1-inhibitors is considered. Much further progress is likely in several of these areas soon.

Original languageEnglish (US)
Pages (from-to)590-601
Number of pages12
JournalHaematologica
Volume96
Issue number4
DOIs
StatePublished - Apr 2011

Keywords

  • JAK2
  • Myeloproliferative neoplasm
  • Ph-negative
  • Ph-positive

ASJC Scopus subject areas

  • Hematology

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    van Etten, R. A., Koschmieder, S., Delhommeau, F., Perrotti, D., Holyoake, T., Pardanani, A., Mesa, R., Green, T., Ibrahim, A. R., Mughal, T., Peter Gale, R., & Goldman, J. (2011). The Ph-positive and Ph-negative myeloproliferative neoplasms: Some topical pre-clinical and clinical issues. Haematologica, 96(4), 590-601. https://doi.org/10.3324/haematol.2010.035675