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Vol. 119, No. 4, 2008
Issue release date: July 2008
Section title: Molecular Drug Targets in Myeloproliferative Neoplasms
Acta Haematol 2008;119:218–225
(DOI:10.1159/000140634)

JAK2 and MPL Mutations in Myeloproliferative Neoplasms

Koppikar P. · Levine R.L.
aHuman Oncology and Pathogenesis Program, bLeukemia Service, Memorial Sloan Kettering Cancer Center, New York, N.Y., USA

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Article / Publication Details

First-Page Preview
Abstract of Molecular Drug Targets in Myeloproliferative Neoplasms

Published online: 6/20/2008

Number of Print Pages: 8
Number of Figures: 0
Number of Tables: 0

ISSN: 0001-5792 (Print)
eISSN: 1421-9662 (Online)

For additional information: http://www.karger.com/AHA

Abstract

The Philadelphia chromosome-negative myeloproliferative disorders (MPDs) polycythemia vera (PV), essential thrombocytosis (ET) and primary myelofibrosis (PMF) are characterized by increased proliferation of terminally differentiated myeloid cells. Although these disorders were recognized as clonal hematopoietic stem cell disorders more than 3 decades ago, little was known about the genetic basis for these disorders until 2005 when a single recurrent mutation in the JAK2 tyrosine kinase (JAK2V617F) was identified in >90% of patients with PV and in a significant proportion of patients with ET and PMF. JAK2V617F is a constitutively active tyrosine kinase and has transforming properties in vitro and in vivo, providing validation JAK2V617F is a bona fide oncogene which contributes to MPD pathogenesis. Subsequent studies of JAK2V617F-negative MPDs have identified mutations in JAK2 exon 12 and MPL, and these mutations also result in constitutive activation of JAK2 signaling. In this review, we will discuss the genetics of PV, ET and PMF with regard to known somatic mutations, the role of these mutations in hematopoietic transformation and the therapeutic implications of these findings.


Article / Publication Details

First-Page Preview
Abstract of Molecular Drug Targets in Myeloproliferative Neoplasms

Published online: 6/20/2008

Number of Print Pages: 8
Number of Figures: 0
Number of Tables: 0

ISSN: 0001-5792 (Print)
eISSN: 1421-9662 (Online)

For additional information: http://www.karger.com/AHA


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Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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