This difference in the effect of JAK2 and MEK inhibitor combination therapy on mutant allele reduction could be due to the different therapeutic models employed—MPN mouse models driven by heterologous promoter overexpression of mutant MPN-driving proteins (e.g. MPL-W515L or JAK2-V617F) versus primary MPN patient cell xenografts. This evidence concerns the gene MPL and myeloproliferative neoplasm.