Signalling pathways activated by all-trans-retinoic acid in acute promyelocytic leukemia cells

Suman Kambhampati, Amit Verma, Yongzhong Li, Simrit Parmar, Antonella Sassano, Leonidas C. Platanias*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

21 Scopus citations

Abstract

Acute promyelocytic leukemia is a form of acute myelogenous leukemia, characterized by the t(15;17) chromososmal translocation and the presence of the abnormal PML-RARα fusion protein. All-transretinoic acid is a potent agent for the treatment of this fatal subtype of AML, and is particularly effective when combined with cytotoxic chemotherapy. The important biological activities of all-transretinoic acid in vitro and in vivo have provoked extensive studies over the years, aimed to define the mechanisms by which it induces its antileukemic effects. It is now well established that all-transretinoic acid when administered at pharmacological doses can reverse the dominant-negative effects that the PML-RARα oncoprotein exhibits on the functions of the wild type PML and RARα proteins. All-trans-retinoic acid induces gene transcription via retinoic acid responsive elements (RARE) that are present in the promoters of retinoid-responsive genes that ultimately result in the production of protein products that regulate leukemic cell differentiation and induce cell-cycle arrest. There is now accumulating evidence that additional signalling pathways are activated during all-trans-retinoic acid-treatment of cells, involving Stat-proteins, tyrosine kinases and mitogen-activated protein (Map) kinases. This review summarizes the current knowledge on the signalling cascades activated by all-trans-retinoic acid in APL cells. The clinical implications and potential translational applications from the accumulating knowledge in the field are also discussed.

Original languageEnglish (US)
Pages (from-to)2175-2185
Number of pages11
JournalLeukemia and Lymphoma
Volume45
Issue number11
DOIs
StatePublished - Nov 1 2004

Keywords

  • Leukemia
  • Map kinase
  • Retinoic acid
  • Tyrosine kinase

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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