Low JAK2V617F allele burden in primary myelofibrosis, compared to either a higher allele burden or unmutated status, is associated with inferior overall and leukemia-free survival

The clinical relevance of JAK2V617F allele burden in primary myelofibrosis (PMF) has not been previously studied. Bone marrow-derived DNA from 199 patients with PMF was subjected to qualitative (n = 199) and quantitative (n=129) analysis for V617F. Mutational frequency was 58% and median mutant allele burden ratio in V617F-positive patients was 29% (range, 1-74%). Multivariable analysis identified older age, platelet count ≥100 × 10⁹l^-1 and peripheral blood blast percentage <3% as being associated with a positive mutational status. The mere presence of the mutation did not affect the incidence of thrombosis (P = 0.78), overall survival (P = 0.22) or leukemia-free survival (P = 0.5). The 129 patients with allele burden information were divided into four groups: V617F-negative (n = 53) and V617F-positive with mutant allele burden in the lower quartile (n = 19), middle quartiles (n = 38) or upper quartile (n = 19) range. Kaplan-Meier plots revealed significantly shortened overall (P = 0.0008) and leukemia-free (P = 0.01) survival for the lower quartile, but not for upper quartile allele burden group; independent prognostic relevance was validated by multivariable analysis. We conclude that low V617F allele burden in PMF might indicate the presence of an overriding V617F-negative clone that confers a more aggressive disease phenotype.