Chronic myeloproliferative disorders: the role of tyrosine kinases in pathogenesis, diagnosis and therapy.
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.
Macdonald
Donald
D
Department of Haematology, Imperial College, London, UK. d.h.mcdonald@imperial.ac.uk
Cross
Nicholas C
NC
D002908:Chronic Disease; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006410:Hematopoiesis / Q000235:genetics; D006801:Humans; D017681:Hypereosinophilic Syndrome / Q000145:classification / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy; D053614:Janus Kinase 2 / Q000235:genetics; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000145:classification / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy; D025202:Molecular Diagnostic Techniques; D050506:Mutant Chimeric Proteins / Q000235:genetics; D009196:Myeloproliferative Disorders / Q000145:classification / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D017354:Point Mutation; D011087:Polycythemia Vera / Q000175:diagnosis / Q000235:genetics / Q000628:therapy; D055728:Primary Myelofibrosis / Q000175:diagnosis / Q000235:genetics / Q000628:therapy; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics; D013920:Thrombocythemia, Essential / Q000175:diagnosis / Q000235:genetics / Q000628:therapy; D039221:mRNA Cleavage and Polyadenylation Factors / Q000235:genetics
D050506:Mutant Chimeric Proteins; D015514:Oncogene Proteins, Fusion; D039221:mRNA Cleavage and Polyadenylation Factors; C496348:FGFR1 protein, human; C479819:FIP1L1-PDGFRA fusion protein, human; D011505:Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; D020796:Receptor, Platelet-Derived Growth Factor alpha; D020797:Receptor, Platelet-Derived Growth Factor beta; C507924:JAK2 protein, human; D053614:Janus Kinase 2