JAK-STAT signaling in the therapeutic landscape of myeloproliferative neoplasms.
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.
Department of Haematology, Guy's and St Thomas' NHS Foundation Trust, London, UK. Electronic address: jennifer.o'sullivan@gstt.nhs.uk.
Jennifer M
JM
O'Sullivan
Department of Haematology, Guy's and St Thomas' NHS Foundation Trust, London, UK.
Claire N
CN
Harrison
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D037282:Calreticulin / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D019337:Hematologic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics* / Q000378:metabolism; D058990:Molecular Targeted Therapy; D022423:Myeloid Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009196:Myeloproliferative Disorders / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009570:Nitriles; D011720:Pyrazoles / Q000627:therapeutic use*; D011743:Pyrimidines; D053628:Receptors, Thrombopoietin / Q000235:genetics / Q000378:metabolism; D050791:STAT Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
D000970:Antineoplastic Agents; C576483:CALR protein, human; D037282:Calreticulin; D009570:Nitriles; D011720:Pyrazoles; D011743:Pyrimidines; D053628:Receptors, Thrombopoietin; D050791:STAT Transcription Factors; C082218:MPL protein, human; C540383:ruxolitinib; C507924:JAK2 protein, human; D053614:Janus Kinase 2
JAK inhibitor; JAK-STAT; Myeloproliferative neoplasm; Primary myelofibrosis; Ruxolitinib