TY - JOUR
T1 - Janus kinases in leukemia
AU - Raivola, Juuli
AU - Haikarainen, Teemu
AU - Abraham, Bobin George
AU - Silvennoinen, Olli
N1 - Funding Information:
Funding: This research was funded by the Academy of Finland, Sigrid Jusélius Foundation, Finnish Cancer Foundation, Jane and Aatos Erkko Foundation, Tampere Tuberculosis Foundation, and Pirkanmaa hospital district competitive research funding.
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021
Y1 - 2021
N2 - Janus kinases (JAKs) transduce signals from dozens of extracellular cytokines and function as critical regulators of cell growth, differentiation, gene expression, and immune responses. Deregulation of JAK/STAT signaling is a central component in several human diseases including various types of leukemia and other malignancies and autoimmune diseases. Different types of leukemia harbor genomic aberrations in all four JAKs (JAK1, JAK2, JAK3, and TYK2), most of which are activating somatic mutations and less frequently translocations resulting in constitutively active JAK fusion proteins. JAKs have become important therapeutic targets and currently, six JAK inhib-itors have been approved by the FDA for the treatment of both autoimmune diseases and hemato-logical malignancies. However, the efficacy of the current drugs is not optimal and the full potential of JAK modulators in leukemia is yet to be harnessed. This review discusses the deregulation of JAK-STAT signaling that underlie the pathogenesis of leukemia, i.e., mutations and other mechanisms causing hyperactive cytokine signaling, as well as JAK inhibitors used in clinic and under clinical development.
AB - Janus kinases (JAKs) transduce signals from dozens of extracellular cytokines and function as critical regulators of cell growth, differentiation, gene expression, and immune responses. Deregulation of JAK/STAT signaling is a central component in several human diseases including various types of leukemia and other malignancies and autoimmune diseases. Different types of leukemia harbor genomic aberrations in all four JAKs (JAK1, JAK2, JAK3, and TYK2), most of which are activating somatic mutations and less frequently translocations resulting in constitutively active JAK fusion proteins. JAKs have become important therapeutic targets and currently, six JAK inhib-itors have been approved by the FDA for the treatment of both autoimmune diseases and hemato-logical malignancies. However, the efficacy of the current drugs is not optimal and the full potential of JAK modulators in leukemia is yet to be harnessed. This review discusses the deregulation of JAK-STAT signaling that underlie the pathogenesis of leukemia, i.e., mutations and other mechanisms causing hyperactive cytokine signaling, as well as JAK inhibitors used in clinic and under clinical development.
KW - Janus kinases
KW - Kinase inhibitor
KW - Leukemia
U2 - 10.3390/cancers13040800
DO - 10.3390/cancers13040800
M3 - Review Article
AN - SCOPUS:85100722916
SN - 2072-6694
VL - 13
SP - 1
EP - 20
JO - Cancers
JF - Cancers
IS - 4
M1 - 800
ER -