TY - JOUR
T1 - Myelofibrosis in 2019
T2 - moving beyond JAK2 inhibition
AU - Schieber, Michael
AU - Crispino, John D.
AU - Stein, Brady
N1 - Funding Information:
B.S. has consulted for Apexx Oncology and Incyte. J.D.C. receives research funding from Scholar Rock and Forma Therapeutics, is a consultant to Sierra Oncology, and is the scientific advisor of the MPN Research Foundation. M.S. declares no conflicts of interest.
Funding Information:
This review was supported in part by grants from the National Institutes of Health HL112792 and the Samuel Waxman Cancer Research Foundation. M.S. is supported by the Physician Scientist Training Program in the Department of Medicine at the McGaw Medical Center of Northwestern University.
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/9/1
Y1 - 2019/9/1
N2 - Myelofibrosis (MF) is a myeloproliferative neoplasm characterized by ineffective clonal hematopoiesis, splenomegaly, bone marrow fibrosis, and the propensity for transformation to acute myeloid leukemia. The discovery of mutations in JAK2, CALR, and MPL have uncovered activated JAK-STAT signaling as a primary driver of MF, supporting a rationale for JAK inhibition. However, JAK inhibition alone is insufficient for long-term remission and offers modest, if any, disease-modifying effects. Given this, there is great interest in identifying mechanisms that cooperate with JAK-STAT signaling to predict disease progression and rationally guide the development of novel therapies. This review outlines the latest discoveries in the biology of MF, discusses current clinical management of patients with MF, and summarizes the ongoing clinical trials that hope to change the landscape of MF treatment.
AB - Myelofibrosis (MF) is a myeloproliferative neoplasm characterized by ineffective clonal hematopoiesis, splenomegaly, bone marrow fibrosis, and the propensity for transformation to acute myeloid leukemia. The discovery of mutations in JAK2, CALR, and MPL have uncovered activated JAK-STAT signaling as a primary driver of MF, supporting a rationale for JAK inhibition. However, JAK inhibition alone is insufficient for long-term remission and offers modest, if any, disease-modifying effects. Given this, there is great interest in identifying mechanisms that cooperate with JAK-STAT signaling to predict disease progression and rationally guide the development of novel therapies. This review outlines the latest discoveries in the biology of MF, discusses current clinical management of patients with MF, and summarizes the ongoing clinical trials that hope to change the landscape of MF treatment.
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U2 - 10.1038/s41408-019-0236-2
DO - 10.1038/s41408-019-0236-2
M3 - Review article
C2 - 31511492
AN - SCOPUS:85072131681
SN - 2044-5385
VL - 9
JO - Blood cancer journal
JF - Blood cancer journal
IS - 9
M1 - 74
ER -