JAK2 and MPL mutations in myeloproliferative neoplasms: Discovery and science Journal Article

  


Authors: Kilpivaara, O.; Levine, R. L.
Article Title: JAK2 and MPL mutations in myeloproliferative neoplasms: Discovery and science
Abstract: Although it has long been known that the myeloproliferative neoplasms (MPN) polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) are clonal hematopoietic stem-cell disorders, for many years the genetic basis for these disorders was elusive. A new era in MPN biology began in 2005 with the discovery of a somatic point mutation in JAK2 tyrosine kinase (JAK2V617F), which was identified in a significant proportion of patients with PV, ET and PMF. Based on the hypothesis that JAK-STAT signaling is central to the pathogenesis of JAK2V617F-negative MPN, genomic studies have identified JAK2 exon 12 mutations in JAK2V617F-negative PV and activating mutations in MPL in patients with JAK2V617F-negative ET and PMF. In this review, we will discuss the role of these mutant alleles in the pathogenesis of PV, ET and PMF, the potential therapeutic implications of these discoveries, and the implications of these discoveries for genomic studies of hematopoietic malignancies.
Keywords: signal transduction; myelofibrosis; unclassified drug; single nucleotide polymorphism; somatic mutation; mutation; myeloproliferative disorder; janus kinase 2; janus kinase inhibitor; thrombopoietin receptor; clinical trial; disease course; myeloid metaplasia; review; cancer growth; cancer risk; drug efficacy; drug safety; nonhuman; drug targeting; pathophysiology; cell proliferation; phenotype; genetic predisposition to disease; enzyme inhibition; gene expression; anemia; amino acid substitution; genetic variability; gene frequency; gene function; enzyme activity; mutational analysis; carcinogenesis; cancer genetics; chromosome aberration; genome analysis; homozygosity; oncogene; uniparental disomy; disease severity; hematologic malignancy; drug research; gene identification; dna sequence; hematopoietic stem cell; heterozygosity loss; gene dosage; malignant transformation; genetic predisposition; genetic screening; leukocytosis; thrombotic thrombocytopenic purpura; pleiotropy; thrombocytosis; polycythemia vera; receptors, thrombopoietin; janus kinase 2 inhibitor; thrombocythemia, hemorrhagic
Journal Title: Leukemia
Volume: 22
Issue: 10
ISSN: 0887-6924
Publisher: Nature Publishing Group  
Date Published: 2008-01-01
Start Page: 1813
End Page: 1817
Language: English
DOI: 10.1038/leu.2008.229
PUBMED: 18754026
PROVIDER: scopus
DOI/URL:

http://www.scopus.com/inward/record.url?eid=2-s2.0-54149085320&partnerID=40&md5=ebeb2753852b35bc61d1eb1a046b529a
Notes: --- - "Cited By (since 1996): 35" - "Export Date: 17 November 2011" - "CODEN: LEUKE" - "Source: Scopus"
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MSK Authors
  1. Ross Levine
    775 Levine
  2. Outi Kilpivaara
    12 Kilpivaara
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