JAK2 and MPL mutations in myeloproliferative neoplasms Journal Article
| Authors: | Koppikar, P.; Levine, R. L. |
| Article Title: | JAK2 and MPL mutations in myeloproliferative neoplasms |
| 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. Copyright © 2008 S. Karger AG. |
| Keywords: | signal transduction; myeloproliferative disorders; chronic myelomonocytic leukemia; somatic mutation; exon; myeloproliferative disorder; exons; mutation, missense; janus kinase 2; myeloid metaplasia; review; chromosome mutation; protein domain; cell proliferation; phenotype; imatinib; gene overexpression; gene expression; amino acid substitution; gene frequency; cytogenetics; cell differentiation; enzyme activation; enzyme activity; protein tyrosine kinase; cell transformation, neoplastic; hematologic neoplasms; hematopoietic stem cells; bone marrow cell; hematopoietic stem cell; bcr abl protein; thrombotic thrombocytopenic purpura; polycythemia vera; systemic mastocytosis; myeloid cells; focal adhesion kinase 1; stat5b protein; genetic transformation; receptors, thrombopoietin; philadelphia chromosome negative cell; jak2; janus kinase 1; mpl mutation; mitogen activated protein kinase 14; stat5a protein; jak3 deficiency |
| Journal Title: | Acta Haematologica |
| Volume: | 119 |
| Issue: | 4 |
| ISSN: | 0001-5792 |
| Publisher: | S. Karger AG |
| Date Published: | 2008-01-01 |
| Start Page: | 218 |
| End Page: | 225 |
| Language: | English |
| DOI: | 10.1159/000140634 |
| PUBMED: | 18566540 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 4" - "Export Date: 17 November 2011" - "CODEN: ACHAA" - "Source: Scopus" |
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