JAK2V617F allele burden discriminates essential thrombocythemia from a subset of prefibrotic-stage primary myelofibrosis

Objective Among Philadelphia chromosome−negative myeloproliferative neoplasms (Ph − MPN), essential thrombocythemia (ET) and the prefibrotic phase of primary myelofibrosis (PMF) represent two subtypes with considerable overlap. Materials and Methods In this study, histopathological classification of 490 MPN cases was correlated with the allelic burden of JAK2 V617F and MPL W515L . Results Ph − MPN entities largely overlap with regard to JAK2 V617F and MPL W515L allele burden, but ET displayed mutant allele burden V617F allele burden. At initial presentation one-quarter of prefibrotic PMF cases exhibited an allele burden exceeding 50% (38% median JAK2 V617F alleles, n=102). In ET, its main differential diagnosis, not a single case was found with >40% JAK2 V617F alleles (median, 24% JAK2 V617F alleles; n=90; p V617F alleles during follow-up could not be linked to fibrosis or blastic progression but was related to polycythemic transformation in ET. MPL W515L was found in 3% of ET and 8% of PMF, with a significantly higher percentage of mutated alleles in fibrotic than prefibrotic PMF (median, 78% MPL W515L alleles; p Conclusion Histopathological categories ET and prefibrotic PMF correlate with significant differences in mutant allelic burden of JAK2 V617F , but not of MPL W515L which, by contrast to JAK2 V617F , shows a higher percentage of mutated alleles in fibrotic than in prefibrotic cases. Thus, for Ph − MPN in which ET and prefibrotic PMF represent the most probable diagnoses, a JAK2 V617F allele burden >50% favors a diagnosis of prefibrotic PMF.