Detection of JAK2 exon 12 mutations in 15 patients with JAK2V617F negative polycythemia vera.
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.
Schnittger
Susanne
S
MLL, Munich Leukemia Laboratory, Max-Lebsche-Platz 31, 81377 Munich, Germany. susanne.schnittger@mll-online.com
Bacher
Ulrike
U
Haferlach
Claudia
C
Geer
Thomas
T
Müller
Peter
P
Mittermüller
Johann
J
Petrides
Petro
P
Schlag
Rudolf
R
Sandner
Reiner
R
Selbach
Johannes
J
Slawik
Hans Rainer
HR
Tessen
Hans Werner
HW
Wehmeyer
Jürgen
J
Kern
Wolfgang
W
Haferlach
Torsten
T
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
C507924:JAK2 protein, human; D053614:Janus Kinase 2