Janus kinases in leukemia

Juuli Raivola; Teemu Haikarainen; Bobin George Abraham; Olli Silvennoinen

doi:10.3390/cancers13040800

Janus kinases in leukemia

Juuli Raivola
, Teemu Haikarainen
, Bobin George Abraham
, Olli Silvennoinen^*

^*Corresponding author for this work

Department of Clinical Microbiology

Research output: Contribution to journal › Review Article › peer-review

45 Citations (Scopus)

15 Downloads (Pure)

Abstract

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.

Original language	English
Article number	800
Pages (from-to)	1-20
Number of pages	20
Journal	Cancers
Volume	13
Issue number	4
DOIs	https://doi.org/10.3390/cancers13040800
Publication status	Published - 2021
Publication type	A2 Review article in a scientific journal

Funding

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.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Janus kinases
Kinase inhibitor
Leukemia

Publication forum classification

Publication forum level 1

ASJC Scopus subject areas

Oncology
Cancer Research

Access to Document

10.3390/cancers13040800Licence: CC BY

cancers-13-00800-v2Final published version, 1.63 MBLicence: CC BY

http://urn.fi/URN:NBN:fi:tuni-202105064553Licence: CC BY

Cite this

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title = "Janus kinases in leukemia",

abstract = "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.",

keywords = "Janus kinases, Kinase inhibitor, Leukemia",

author = "Juuli Raivola and Teemu Haikarainen and Abraham, \{Bobin George\} and Olli Silvennoinen",

note = "Funding Information: Funding: This research was funded by the Academy of Finland, Sigrid Jus{\'e}lius Foundation, Finnish Cancer Foundation, Jane and Aatos Erkko Foundation, Tampere Tuberculosis Foundation, and Pirkanmaa hospital district competitive research funding. Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2021",

doi = "10.3390/cancers13040800",

language = "English",

volume = "13",

pages = "1--20",

journal = "Cancers",

issn = "2072-6694",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "4",

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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 -

Janus kinases in leukemia

Abstract

Funding

UN SDGs

Keywords

Publication forum classification

ASJC Scopus subject areas

Access to Document

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Cite this