In this study, histopathological classification of 490 MPN cases was correlated with the allelic burden of JAK2V617F and MPLW515L.
Ph− MPN entities largely overlap with regard to JAK2V617F and MPLW515L allele burden, but ET displayed mutant allele burden <50 % . PMF with different stages of myelofibrosis all yielded similar JAK2V617F allele burden. At initial presentation one-quarter of prefibrotic PMF cases exhibited an allele burden exceeding 50 % (38 % median JAK2V617F alleles, n = 102). In ET, its main differential diagnosis, not a single case was found with >40 % JAK2V617F alleles (median, 24 % JAK2V617F alleles; n = 90; p < 0.001). Increase in JAK2V617F 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).
Histopathological categories ET and prefibrotic PMF correlate with significant differences in mutant allelic burden of JAK2V617F, but not of MPLW515L which, by contrast to JAK2V617F, 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 JAK2V617F allele burden >50 % favors a diagnosis of prefibrotic PMF.