JAK3: a two-faced player in hematological disorders

Int J Biochem Cell Biol. 2009 Dec;41(12):2376-9. doi: 10.1016/j.biocel.2009.09.004. Epub 2009 Sep 9.

Abstract

JAK3 is a non-receptor tyrosine kinase, predominantly expressed in hematopoietic cells and that has been implicated in the signal transduction of the common gamma chain subfamily of cytokine receptors. As a result, JAK3 plays an essential role in hematopoieisis during T cell development. JAK3 inactivating mutations result in immunodeficiency syndromes (SCID) in both humans and mice. Recent data indicate that abnormal activation of JAK3 due to activating mutations is also found in human hematological malignancies, including acute megakaryoblastic leukemia (AMKL) and cutaneous T cell lymphoma (CTCL). After a brief summary of the JAK3 structure and function, we will review the evidence on the emerging role of JAK3 activation in hematological malignancies that warrant further studies to test the relevance of specific inhibition of JAK3 as a therapeutic approach to these challenging clinical entities.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Gene Expression Regulation, Neoplastic
  • Hematologic Neoplasms / drug therapy
  • Hematologic Neoplasms / immunology*
  • Humans
  • Interleukin Receptor Common gamma Subunit / metabolism*
  • Janus Kinase 3 / genetics
  • Janus Kinase 3 / immunology
  • Janus Kinase 3 / metabolism*
  • Lymphocytes / immunology
  • Mice
  • Piperidines
  • Pyrimidines / therapeutic use
  • Pyrroles / therapeutic use
  • Receptors, Cytokine / metabolism*
  • Signal Transduction

Substances

  • Interleukin Receptor Common gamma Subunit
  • Piperidines
  • Pyrimidines
  • Pyrroles
  • Receptors, Cytokine
  • tofacitinib
  • Janus Kinase 3