Clinical correlates of JAK2V617F allele burden in essential thrombocythemia

BACKGROUND. JAK2V617F occurs in approximately 50% of patients with essential thrombocythemia (ET). Qualitative studies of mutation analysis have previously reported an association between JAK2V617F and advanced age, higher hemoglobin level, higher leukocyte count, and lower platelet count. A possible association with thrombotic complication has also been considered. METHODS. Allele-specific, quantitative polymerase chain reaction (PCR) analysis for JAK2V617F was performed in 176 patients with ET using genomic DNA from archived bone marrow, which was collected within 1 year (n = 72 patients), between 1 and 5 years (n = 64 patients), or after 5 years (n = 40 patients) of diagnosis. RESULTS. JAK2V617F was detected in 96 patients (55%), in whom mutant allele burden ranged from 1% to 100% (median, 6.3%). Neither mutational frequency (P = .37) nor mutant allele burden (P = .62) was affected by the timing of bone marrow sample collection. The presence of JAK2V617F was found to be significantly associated with higher hemoglobin level (P < .0001), lower platelet count (P = .001), higher leukocyte count (P = .008), increased incidence of venous thrombosis occurring after diagnosis (P = .02), and older age at diagnosis (P = .03). All but age retained significance in multivariable analysis. In mutation-positive patients (n = 96 patients), JAK2V617F allele burden clustered between 1% and 22% in 94 cases, in whom it correlated directly and significantly with platelet and leukocyte counts, palpable splenomegaly at diagnosis, and venous thrombosis occurring after diagnosis. The latter 2 associations remained significant with the inclusion of the remaining 2 outlier cases with 100% mutant allele burden; in addition, an association with male gender became evident. CONCLUSIONS. JAK2V617F allele burden imparts additional phenotypic effects in ET.