Open AccessSelective Inhibition of JAK1 Primes STAT5-Driven Human Leukemia Cells for ATRA-Induced Differentiation
Author(s) -
Haley E. Ramsey,
Kristy R. Stengel,
James C. Pino,
Gretchen Johnston,
Merrida Childress,
Agnieszka E. Gorska,
Pia Arrate,
Londa Fuller,
Matthew T. Villaume,
Melissa A. Fischer,
P. Brent Ferrell,
Caroline E. Roe,
Jing Zou,
Alexander L R Lubbock,
Matthew C. Stubbs,
Sandra S. Zinkel,
Jonathan M. Irish,
Carlos F. López,
Scott W. Hiebert,
Michael R. Savona
Publication year - 2021
Publication title -
targeted oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.697
H-Index - 40
eISSN - 1776-260X
pISSN - 1776-2596
DOI - 10.1007/s11523-021-00830-5
Subject(s) - ruxolitinib , myelofibrosis , medicine , cancer research , acute promyelocytic leukemia , in vivo , leukemia , differentiation therapy , myeloid , myeloid leukemia , stat3 , cell culture , retinoic acid , immunology , signal transduction , bone marrow , biology , microbiology and biotechnology , genetics
All-trans retinoic acid (ATRA), a derivate of vitamin A, has been successfully used as a therapy to induce differentiation in M3 acute promyelocytic leukemia (APML), and has led to marked improvement in outcomes. Previously, attempts to use ATRA in non-APML in the clinic, however, have been underwhelming, likely due to persistent signaling through other oncogenic drivers. Dysregulated JAK/STAT signaling is known to drive several hematologic malignancies, and targeting JAK1 and JAK2 with the JAK1/JAK2 inhibitor ruxolitinib has led to improvement in survival in primary myelofibrosis and alleviation of vasomotor symptoms and splenomegaly in polycythemia vera and myelofibrosis.