Signaling via the interferon-α receptor in chronic myelogenous leukemia cells

Amit K. Verma, Leonidas C. Platanias

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

It is well established that IFNα has significant clinical activity in the treatment of chronic myelogenous leukemia (CML). This cytokine has been used for many years in the management of patients in the chronic phase of the disease, but the mechanisms by which it induces growth inhibitory effects in CML-cells have not been elucidated. Understanding the signaling mechanisms by which the Type I IFN receptor transduces growth inhibitory signals in BCR-ABL expressing cells should prove very valuable, as it may result in the design of new, more specific pharmacological compounds that target the same cellular cascades. Recent evidence indicates that, in addition to the classic IFN-activated Jak-Stat pathway, the Type I IFN receptor engages in its signaling cascade the CrkL-adapter protein, which is also a substrate for the kinase activity of the BCR-ABL oncogene. In addition, it appears that activation of a member of the Map kinase (MAPK) family of proteins, the p38 MAPK, is essential for the generation of the antileukemic effects of IFNα. This review summarizes the recent advances in the field of interferon signaling in CML cells and discusses the implications of identifying signaling proteins that mediate IFNα-induced growth inhibition.

Original languageEnglish (US)
Pages (from-to)703-709
Number of pages7
JournalLeukemia and Lymphoma
Volume43
Issue number4
DOIs
StatePublished - 2002
Externally publishedYes

Fingerprint

Interferon Receptors
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Phosphotransferases
Growth
Cohort Effect
p38 Mitogen-Activated Protein Kinases
Oncogenes
Interferons
Proteins
Chronic Disease
Pharmacology
Cytokines
Therapeutics

Keywords

  • CrkL
  • Interferon
  • Jak kinases
  • Map kinase
  • Signal transduction
  • Stats

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Signaling via the interferon-α receptor in chronic myelogenous leukemia cells. / Verma, Amit K.; Platanias, Leonidas C.

In: Leukemia and Lymphoma, Vol. 43, No. 4, 2002, p. 703-709.

Research output: Contribution to journalArticle

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