1-PDGFRB

1-PDGFRB - Leukemia(2002 16 1207–1212 2002 Nature...

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Unformatted text preview: Leukemia (2002) 16 , 1207–1212 2002 Nature Publishing Group All rights reserved 0887-6924/02 $25.00 www.nature.com/leu POTLIGHT REVIEW Tyrosine kinase fusion genes in chronic myeloproliferative diseases NCP Cross 1 and A Reiter 2 1 Wessex Regional Genetics Laboratory, Salisbury, UK and Human Genetics Division, University of Southampton, UK; and 2 III Medizinische Universita ¨tsklinik, Klinikum Mannheim, Fakulta ¨t fu ¨r Klinische Medizin der Universita ¨t Heidelberg, Germany With the exception of chronic myeloid leukemia (CML), chronic myeloproliferative disorders (CMPDs) are a heterogeneous spectrum of conditions for which the molecular pathogenesis is not well understood. Most cases have a normal or aneuploid karyotype, but a minority present with a reciprocal translo- cation that disrupts specific tyrosine kinase genes, most com- monly PDGFRB or FGFR1. These translocations result in the production of constitutively active tyrosine kinase fusion pro- teins that deregulate hemopoiesis in a manner analogous to BCR-ABL. With the advent of targeted signal transduction ther- apy, an accurate clinical and molecular diagnosis of CMPDs has become increasingly important. Currently, patients with PDGFRB or ABL fusion genes are candidates for treatment with Imatinib (STI571), but it is likely that alternative strategies will be necessary for the treatment of most other patients. Leukemia (2002) 16, 1207–1212. doi:10.1038/sj.leu.240556 Keywords: tyrosine kinase; myeloproliferative disorders; ABL; FGFR1; PDGFRB; JAK2 Introduction The chronic myeloproliferative diseases (CMPD) are clonal disorders characterized by excess proliferation of cells from one or more myeloid lineages. Proliferation is accompanied by relatively normal maturation, resulting in increased num- bers of granulocytes, red blood cells and/or platelets in the peripheral blood. Some patients also show dysplastic features and are considered to have a related condition termed myelodysplastic/myeloproliferative disease (MDS/MPD). 1 Below we use the term ‘MPD’ to encompass all patients with myeloproliferative features, ie either CMPD or MDS/MPD. The most common CMPD is chronic myelogenous leuke- mia (CML), a disease that has been reviewed in detail recently. 2,3 CML is characterized by the presence of the BCR- ABL fusion gene in all myeloid lineage cell types, as well as in some lymphoid cells. The BCR-ABL chimeric protein is a deregulated, constitutively active tyrosine kinase that is believed to be the primary, and possibly the only driving force behind the disease. Bone marrow-derived metaphases from approximately 90% of CML cases harbor the t(9;22)(q34;q11.2), the smaller derivative of which is known as the Philadelphia (Ph) chromosome. The remaining patients either have a cryptic translocation between BCR and ABL that cannot be detected by routine cytogenetic analysis, or they have a complex translocation that involves a third or more chromosomes in addition to chromosomes 9 and 22.chromosomes in addition to chromosomes 9 and 22....
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1-PDGFRB - Leukemia(2002 16 1207–1212 2002 Nature...

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