Oncogenic mechanisms in myeloproliferative disorders

Cell Mol Life Sci. 2006 Dec;63(24):2939-53. doi: 10.1007/s00018-006-6272-7.

Abstract

Myeloproliferative disorders (MPDs) are clonal haematopoietic malignancies involving the abnormal proliferation of myeloid lineages. The World Health Organisation (WHO) classification of haematopoietic malignancies distinguishes MPDs from myelodysplastic/ myeloproliferative disorders and systemic mastocytosis. These malignancies frequently involve constitutive tyrosine kinase activity, resulting from either oncogenic fusion protein production or from point mutations. Chronic myelogenous leukaemia is the model used for studies of the consequences of such molecular defects. However, the heterogeneity of the clinical course of MPDs should be seen in a more rationale conceptual framework, including the many molecular events associated with these diseases. This review focuses on the various tyrosine kinase-related molecular mechanisms underlying both MPDs and rare diseases with myeloproliferative features. We pay particular attention to the newly identified JAK2 V617F mutation in polycythaemia vera, essential thrombocythaemia and idiopathic myelofibrosis and deal with disease heterogeneity and putative additional molecular mechanisms.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Genes, abl*
  • Genetic Predisposition to Disease
  • Humans
  • Janus Kinase 2 / genetics
  • Janus Kinase 2 / metabolism
  • Mastocytosis / genetics
  • Myeloproliferative Disorders / diagnosis
  • Myeloproliferative Disorders / genetics*
  • Myeloproliferative Disorders / metabolism
  • Point Mutation
  • Protein-Tyrosine Kinases / genetics*
  • Protein-Tyrosine Kinases / metabolism
  • Proto-Oncogene Proteins c-kit / genetics
  • Rare Diseases / genetics
  • Rare Diseases / metabolism
  • Receptor, Fibroblast Growth Factor, Type 1 / genetics
  • Receptor, Platelet-Derived Growth Factor beta / genetics
  • Signal Transduction*
  • mRNA Cleavage and Polyadenylation Factors / genetics

Substances

  • FIP1L1 protein, human
  • mRNA Cleavage and Polyadenylation Factors
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins c-kit
  • Receptor, Fibroblast Growth Factor, Type 1
  • Receptor, Platelet-Derived Growth Factor beta
  • Janus Kinase 2