title: Detection of JAK2 exon 12 mutations in 15 patients with JAK2V617F negative polycythemia vera.
abstract: To further characterize JAK2 exon 12 mutations, we performed molecular screening in 409 patients with polycythemia vera or unclear erythrocytosis with unmutated JAK2V617. The frequency of JAK2exon12 mutations was 10/63 (15.9%) in PV but only 5/346 (1.4%) in the erythrocytosis cases. Nine different mutations including four new types (D544-L545del, H538DK539LI540S, H538-K539del, V536-F547dup) were detected. In 2 cases we found evidence for the presence of cells homozygous for mutated JAK2exon12. As this was the case in only 2/15 cases with JAK2exon12 mutations (13%) homozygosity seemed to be less frequent than in V617F-mutated polycythemia vera (69%) (p<0.001). There were more females than males in the group of patients with a JAK2exon12 mutation (10 vs. 5) compared to the group with wildtype JAK2 (132 vs. 262; p=0.012). Median age of onset was lower than in the V617Fmut controls (58.5 vs. 67.8 years, p<0.001). In conclusion, JAK2 exon 12 mutation analysis contributes to diagnostics in polycythemia vera or erythrocytosis.
authors.affiliation: MLL, Munich Leukemia Laboratory, Max-Lebsche-Platz 31, 81377 Munich, Germany. susanne.schnittger@mll-online.com
authors.forename: Susanne
authors.initials: S
authors.lastname: Schnittger
authors.forename: Ulrike
authors.initials: U
authors.lastname: Bacher
authors.forename: Claudia
authors.initials: C
authors.lastname: Haferlach
authors.forename: Thomas
authors.initials: T
authors.lastname: Geer
authors.forename: Peter
authors.initials: P
authors.lastname: Müller
authors.forename: Johann
authors.initials: J
authors.lastname: Mittermüller
authors.forename: Petro
authors.initials: P
authors.lastname: Petrides
authors.forename: Rudolf
authors.initials: R
authors.lastname: Schlag
authors.forename: Reiner
authors.initials: R
authors.lastname: Sandner
authors.forename: Johannes
authors.initials: J
authors.lastname: Selbach
authors.forename: Hans Rainer
authors.initials: HR
authors.lastname: Slawik
authors.forename: Hans Werner
authors.initials: HW
authors.lastname: Tessen
authors.forename: Jürgen
authors.initials: J
authors.lastname: Wehmeyer
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kern
authors.forename: Torsten
authors.initials: T
authors.lastname: Haferlach
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020125:Mutation, Missense; D011086:Polycythemia / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D011087:Polycythemia Vera / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D055815:Young Adult
chemical_list: C507924:JAK2 protein, human; D053614:Janus Kinase 2