Novel therapies for myelofibrosis.

Abstract:

:Myelofibrosis (MF), including primary, post-essential thrombocythemia and post-polycythemia vera MF, associates with a reduced quality of life and shortened life expectancy. Dysregulation of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway is prominent, even in the absence of the JAK2(V617F) mutation. Therefore, all symptomatic MF patients may potentially derive benefit from JAK inhibitors. Despite the efficacy of JAK inhibitors in controlling signs and symptoms of MF, they do not eradicate the disease. Therefore, JAK inhibitors are currently being tested in combination with other novel therapies, a strategy which may be more effective in reducing disease burden, either by overcoming JAK inhibitor resistance or targeting additional mechanisms of pathogenesis. Additional targets include modulators of epigenetic regulation, pathways that work downstream from JAK/STAT (i.e. mammalian target of rapamycin/AKT/phosphoinositide 3-kinase) heat shock protein 90, hedgehog signaling, pro-fibrotic factors, abnormal megakaryocytes and telomerase. In this review, we discuss novel MF therapeutic strategies.

journal_name

Leuk Lymphoma

journal_title

Leukemia & lymphoma

authors

Stein BL,Cervantes F,Giles F,Harrison CN,Verstovsek S

doi

10.3109/10428194.2015.1037762

subject

Has Abstract

pub_date

2015-01-01 00:00:00

pages

2768-78

issue

10

eissn

1042-8194

issn

1029-2403

journal_volume

56

pub_type

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