Janus Kinases in Leukemia.

Autor: Raivola J; Faculty of Medicine and Health Technology, Tampere University, 33014 Tampere, Finland., Haikarainen T; Faculty of Medicine and Health Technology, Tampere University, 33014 Tampere, Finland., Abraham BG; Faculty of Medicine and Health Technology, Tampere University, 33014 Tampere, Finland., Silvennoinen O; Faculty of Medicine and Health Technology, Tampere University, 33014 Tampere, Finland.; Institute of Biotechnology, Helsinki Institute of Life Science HiLIFE, University of Helsinki, 00014 Helsinki, Finland.; Fimlab Laboratories, Fimlab, 33520 Tampere, Finland.
Jazyk: angličtina
Zdroj: Cancers [Cancers (Basel)] 2021 Feb 14; Vol. 13 (4). Date of Electronic Publication: 2021 Feb 14.
DOI: 10.3390/cancers13040800
Abstrakt: 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 inhibitors have been approved by the FDA for the treatment of both autoimmune diseases and hematological 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.
Databáze: MEDLINE
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