The clinical phenotype of wild-type, heterozygous, and homozygous JAK2 ^V617F in polycythemia vera

BACKGROUND. Several studies have recently reported on the occurrence of a JAK2^V617F mutation in myeloid cells from the majority of patients with polycythemia vera (PV). The clinical relevance of this novel observation currently is under study. METHODS. In a single institutional study, mutation screening for JAK2^V617F was performed in DNA derived from archived blood granulocytes from 63 consecutive patients with PV in whom current diagnostic criteria were strictly applied and the diagnosis confirmed by bone marrow histology. RESULTS. The JAK2^V617F mutant allele was detected in 58 of the 63 patients (92%) with 21% homozygosity. The clinical phenotype of the five patients with the wild-type allele was otherwise typical for the disease. A statistical comparison between JAK2^V617F heterozygotes (n = 45 patients) and homozygotes (n = 13 patients) did not reveal any significant associations with regard to age, gender, leukocyte or platelet count at the time of diagnosis, duration of disease, or the incidences of thrombosis or bleeding. However, compared with their heterozygote counterparts, JAK2^V617F homozygote patients displayed a significantly higher hemoglobin level at the time of diagnosis (P = 0.001), an increased incidence of pruritus (69% vs. 38%; P = 0.04), a higher rate of fibrotic transformation (23% vs. 2%; P = 0.009), and higher PRV-1 transcript levels in their blood granulocytes (P = 0.07). CONCLUSIONS. The results of the current clinical study support previous laboratory observations that link JAK2^V617F with the PV phenotype by demonstrating a mutant allele dose effect on erythrocytosis and clinical and laboratory features characteristic of PV.