Increased frequency of co-existing JAK2 exon-12 or MPL exon-10 mutations in patients with low JAK2^V617F allelic burden

The frequency of co-existing JAK2^V617F/MPL and JAK2^V617F/JAK2 exon-12 mutations has not been previously investigated in MPNs. Poor survival was reported in primary myelofibrosis with low JAK2^V617F allelic burden. However, mutational status of JAK2 exon-12 or MPL were not reported in these patients. This study developed a cost-effective multiplex high resolution melt assay that screens for mutations in JAK2 gene exons-12 and -14 (^V617F) and MPL gene exon-10. Co-existing mutations with JAK2^V617F were detected in 2.9% (6/208; two JAK2 exon-12 and four MPL exon-10) patient specimens with known JAK2^V617F (allelic-burden range: 0.1-96.8%). Co-existing mutations were detected in specimens with < 12% JAK2^V617F allelic burden. Current WHO guidelines do not recommend further testing once JAK2^V617F mutation is detected in MPNs. The findings, however, indicate that quantification of JAK2^V617F allele burden may be clinically relevant in MPNs and in those with low allelic burden additional testing for JAK2 exon-12 and MPL exon-10 mutation should be pursued.