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Aberrant signal transduction pathways in myeloproliferative neoplasms

Leukemia volume 22, pages 1828–1840 (2008)Cite this article

Abstract

The BCR-ABL-negative myeloproliferative neoplasms (MPNs), polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF), entered the spotlight in 2005 when the unique somatic acquired JAK2 V617F mutation was described in >95% of PV and in 50% of ET and PMF patients. For the very rare PV patients who do not harbor the JAK2 V617F mutation, exon 12 JAK2 mutants were discovered also to result in activated forms of JAK2. A minority of ET and PMF patients harbor mutations that constitutively activate the thrombopoietin receptor (TpoR). In bone marrow reconstitution models based on retroviral transduction, the phenotype induced by JAK2 V617F is less severe and different from the rapid fatal myelofibrosis induced by TpoR W515L. The reasons for these differences are unknown. Exactly by which mechanism(s) one acquired somatic mutation, JAK2 V617F, can promote three different diseases remains a mystery, although gene dosage and host genetic variation might have important functions. We review the recent progress made in deciphering signaling anomalies in PV, ET and PMF, with an emphasis on the relationship between JAK2 V617F and cytokine receptor signaling and on cross-talk with several other signaling pathways.

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Acknowledgements

We are grateful to William Vainchenker, Jean-Christophe Renauld, Laurent Knoops and Ross Levine for stimulating discussions. We thank the Fondation Salus Sanguinis, the Action de Recherche Concertée (ARC) MEXP31 of the Université Catholique de Louvain, the Fondation contre le cancer, the Atlantic Philanthropies, New York, and the de Duve Institute for generous support. JK is supported by the Haas-Teichen Postdoctoral Fellowship of the de Duve Institute. SNC is a Research Associate and recipient of a Mandat d’Impulsion of the Fonds National de la Recherche Scientifique (FNRS), Belgium.

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  1. Signal Transduction Laboratory, Brussels Branch of Cancer Genetics, Ludwig Institute for Cancer Research and de Duve Institute, Université Catholique de Louvain, Brussels, Belgium

    J Kota, N Caceres & S N Constantinescu

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Kota, J., Caceres, N. & Constantinescu, S. Aberrant signal transduction pathways in myeloproliferative neoplasms. Leukemia 22, 1828–1840 (2008). https://doi.org/10.1038/leu.2008.236

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