title: The JAK2-V617F mutation is frequently present at diagnosis in patients with essential thrombocythemia and polycythemia vera.
abstract: We determined the allelic frequency of the JAK2-V617F mutation in DNA and assessed the expression levels of the mutant and wild-type JAK2 mRNA in granulocytes from 60 patients with essential thrombocythemia (ET) and 62 patients with polycythemia vera (PV) at the time of diagnosis. Using allele-specific quantitative polymerase chain reaction (qPCR), we detected JAK2-V617F in 75% of ET and 97% of PV at diagnosis. The total JAK2 mRNA levels were elevated in ET, PV, and secondary and idiopathic erythrocytosis, suggesting that hyperactive hematopoiesis alters JAK2 expression. The expression levels of JAK2-V617F mRNA were variable but strongly correlated with the allelic ratio of JAK2-V617F determined in DNA. Thus, differences in JAK2-V617F expression, markedly lower in ET than in PV, reflected different percentages of granulocytes carrying the mutation. Moreover, allelic ratios higher than 50% JAK2-V617F, indicating the presence of granulocytes homozygous for JAK2-V617F, were found in 70% of PV at diagnosis but never in ET.
authors.affiliation: Laboratoire d'Hématologie du CHU de Bourdeaux, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Lippert
authors.forename: Marjorie
authors.initials: M
authors.lastname: Boissinot
authors.forename: Robert
authors.initials: R
authors.lastname: Kralovics
authors.forename: François
authors.initials: F
authors.lastname: Girodon
authors.forename: Irène
authors.initials: I
authors.lastname: Dobo
authors.forename: Vincent
authors.initials: V
authors.lastname: Praloran
authors.forename: Nathalie
authors.initials: N
authors.lastname: Boiret-Dupré
authors.forename: Radek C
authors.initials: RC
authors.lastname: Skoda
authors.forename: Sylvie
authors.initials: S
authors.lastname: Hermouet
mesh_terms: D000483:Alleles; D019943:Amino Acid Substitution; D001483:Base Sequence; D004247:DNA / Q000235:genetics; D005787:Gene Frequency; D006098:Granulocytes / Q000378:metabolism; D006801:Humans; D053614:Janus Kinase 2; D010641:Phenotype; D017354:Point Mutation; D011087:Polycythemia Vera / Q000175:diagnosis / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013920:Thrombocythemia, Essential / Q000175:diagnosis / Q000235:genetics*
chemical_list: D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D004247:DNA; D011505:Protein-Tyrosine Kinases; C507924:JAK2 protein, human; D053614:Janus Kinase 2