Pathogenesis of myeloproliferative neoplasms: insights from mouse models

Abstract

One of the main molecular features of myeloproliferative neoplasms (MPNs) is the high frequency of JAK2V617F or CALRexon 9 mutations. The mouse models driven by these mutations suggest that they are the direct cause of MPNs and that the expression levels of mutated genes define the disease phenotype. The function of MPN-initiating cells was also elucidated using these mouse models. Furthermore, these mouse models play important roles as disease models to investigate the effects and mechanisms of action of therapeutic drugs such as JAK2 inhibitors and interferon α against MPNs. The mutation landscape of hematological tumors has already been clarified using next-generation sequencing technology, and future research on the importance of the functional analysis of mutant genes in vivo should be emphasized. Thus, it is necessary to promote rapid genetic modification techniques such as genome editing.