Chronic Myeloproliferative Disorders: The Role of Tyrosine Kinases in Pathogenesis, Diagnosis and TherapyMacdonald D.a · Cross N.C.b
aDepartment of Haematology, Imperial College, London, and bWessex Regional Genetics Laboratory, University of Southampton, Salisbury Hospital, Salisbury, UK
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The term chronic myeloproliferative disorders was originally used by Damashek to describe the link amongst a group of acquired blood diseases. Recent molecular genetic analysis has provided a scientific basis for this observation. Underlying myeloproliferative disorders are acquired abnormalities of tyrosine kinase genes. These may be chromosomal translocations resulting in the creation of a fusion kinase gene, examples of which include ABL, FGFR, and PDGFR as seen in disorders CML, 8p11 myeloproliferative syndrome, atypical CML and chronic eosinophilic leukaemia. The second group of tyrosine kinase abnormalities are point mutations in JAK2, a cytosolic TK. This abnormality is seen in 30–97% of cases of MPD with the phenotype PV, ET or CIMF.
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