The role of driver mutations in myeloproliferative neoplasms: insights from mouse models.

Abstract

High frequency of JAK2V617F or CALR exon 9 mutations is a main molecular feature of myeloproliferative neoplasms (MPNs). Analysis of mouse models driven by these mutations suggests that they are a direct cause of MPNs and that the expression levels of the mutated genes define the disease phenotype. The function of MPN-initiating cells has also been elucidated by these mouse models. Such mouse models also play an important role in modeling disease to investigate the effects and action mechanisms of therapeutic drugs, such as JAK2 inhibitors and interferon α, against MPNs. The mutation landscape of hematological tumors has already been clarified by next-generation sequencing technology, and the importance of functional analysis of mutant genes in vivo should increase further in the future.