[New molecular markers within the chronic myeloproliferative disorders. II: the JAK2 mutation].
The Philadelphia-negative chronic myeloproliferative disorders feature autonomous myeloid hyperproliferation and hypersensitivity to a number of growth factors, which most recently have been shown to be explained by a guanine-to-thymidine mutation in the Janus tyrosine kinase (JAK2) gene, implicating that phenylalanine is substituted with valine in position 617 (V617F mutation). JAK2 is of particular importance to haematopoiesis, since JAK2 proteins are activated mainly by the haematopoietic growth factors. The JAK2 mutation is present in most patients with polycythaemia vera and about 50% of patients with essential thrombocytosis and idiopathic myelofibrosis. The identification of the JAK2 mutation is a major molecular breakthrough in the understanding of the pathobiology of these disorders, and it is a new molecular marker to be used in the future classification of the diseases as well as a simple and rapid diagnostic test. The mutated JAK2 tyrosine kinase is an obvious potential target for a small-molecule inhibitor of tyrosine kinase activity.
Larsen
Thomas Stauffer
TS
Odense Universitetshospital, Patologisk Institut og Haematologisk Afdeling X. thomas.stauffer.larsen@ouh.fyns-amt.dk
Pallisgaard
Niels
N
Christensen
Jacob Haaber
JH
Gram-Hansen
Paul
P
Kerndrup
Gitte B
GB
Møller
Michael Boe
MB
Hasselbalch
Hans Carl
HC
D015415:Biomarkers / Q000097:blood*; D004252:DNA Mutational Analysis; D006801:Humans; D053614:Janus Kinase 2; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics; D009154:Mutation; D009196:Myeloproliferative Disorders / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D010677:Philadelphia Chromosome; D011087:Polycythemia Vera / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics; D055728:Primary Myelofibrosis / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics; D011379:Prognosis; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000235:genetics*; D015398:Signal Transduction; D013922:Thrombocytosis / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics
D015415:Biomarkers; D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; C507924:JAK2 protein, human; D053614:Janus Kinase 2