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 MPLW515L. Results. Ph- MPN entities largely overlap with regard to JAK2(V617F) and MpL(W5151) allele burden, but ET displayed mutant allele burden <50%. PMF with different stages of myelofibrosis all yielded similar JAK2(V617F) allele burden. At initial presentation one-quarter of prefibrotic PMF JAK2(V617F) alleles, n = 102). In ET, cases exhibited an allele burden exceeding 50% (38% median JAK2(V617F) its main differential diagnosis, not a single case was found with >40% JAK2(V617F) alleles (median, 24% JAK2(V617F) alleles; n = 90; p < 0.001). Increase in JAK2(V617F) alleles during follow-up could not be linked to fibrosis or blastic progression but was related to polycythemic transformation in ET.MPLW515L 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% MPLW515L alleles; p < 0.05). Conclusion. Histopathological categories ET and prefibrotic PMF correlate with significant differences in mutant allelic burden of JAK2(V617F), but not of MPLW515L 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. (C) 2009 ISEH -Society for Hematology and Stem Cells. Published by Elsevier Inc.