JAK-STAT signaling in the therapeutic landscape of myeloproliferative neoplasms

JM O'Sullivan, CN Harrison - Molecular and cellular endocrinology, 2017 - Elsevier
JM O'Sullivan, CN Harrison
Molecular and cellular endocrinology, 2017Elsevier
Myeloproliferative neoplasms (MPN) are a group of disorders defined by clonal proliferation
of mature myeloid cells with overlapping clinical features. The driver mutations of these
disorders, namely JAK2 (Janus Kinase), MPL (Myeloproliferative Leukaemia Virus) and
CALR (Calreticulin) upregulate JAK-STAT signaling with increase in downstream
transcription and gene expression. Epigenetic mutations are prevalent in MPNs but their
interplay with aberrant JAK-STAT signaling is not known. This understanding lead to …
Abstract
Myeloproliferative neoplasms (MPN) are a group of disorders defined by clonal proliferation of mature myeloid cells with overlapping clinical features. The driver mutations of these disorders, namely JAK2 (Janus Kinase), MPL (Myeloproliferative Leukaemia Virus) and CALR (Calreticulin) upregulate JAK-STAT signaling with increase in downstream transcription and gene expression. Epigenetic mutations are prevalent in MPNs but their interplay with aberrant JAK-STAT signaling is not known. This understanding lead to development of first targeted treatment in MPN; ruxolitinib for primary myelofibrosis. This has shown clinical benefit in overall survival and symptoms improvement but has yet to show significant disease modifying effects. This review will focus on contemporaneous understanding of altered JAK-STAT signaling in MPN and targeted treatments in clinical practice.
Elsevier