Chronic myeloproliferative disorders: a tyrosine kinase tale.
Chronic myeloproliferative diseases (CMPDs) are characterized by the abnormal proliferation and survival of one or more myeloid cell types. The archetype of this class of hematological diseases is chronic myeloid leukemia (CML), characterized by the presence of the Philadelphia (Ph) chromosome, the result of t(9;22)(q34;q11), and the associated BCR-ABL1 oncogene. Some of the Ph-negative myeloproliferative diseases are characterized by other chromosomal translocations involving a variety of tyrosine kinase genes, including ABL1, ABL2, PDGFRA, PDGFRB, FGFR1, and JAK2. The majority of Ph-negative CMPDs, however, such as chronic eosinophilic leukemia, polycythemia vera, essential thrombocythemia, and idiopathic myelofibrosis are not characterized by the presence of recurrent chromosomal abnormalities. Recent studies have identified the FIP1L1-PDGFRA fusion gene, generated due to a small cryptic deletion on chromosome 4q12, and the activating V617F mutation in JAK2 in a significant fraction of Ph-negative CMPDs. These results show that abnormalities in tyrosine kinase genes are central to the molecular pathogenesis of CMPDs. Genome-wide screenings to identify novel tyrosine kinase abnormalities in CMPDs may contribute to further improvement of the diagnosis and the treatment of these diseases.
De Keersmaecker
K
K
Department of Human Genetics, Flanders Interuniversity Institute for Biotechnology (VIB), University of Leuven, Leuven, Belgium.
Cools
J
J
D002869:Chromosome Aberrations; D002908:Chronic Disease; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000201:enzymology* / Q000235:genetics*; D009154:Mutation; D009196:Myeloproliferative Disorders / Q000201:enzymology* / Q000235:genetics*; D010677:Philadelphia Chromosome; D011505:Protein-Tyrosine Kinases / Q000235:genetics*
D011505:Protein-Tyrosine Kinases