Apoptosis induction by retinoids in eosinophilic leukemia cells: Implication of retinoic acid receptor-α signaling in all-trans-retinoic acid hypersensitivity

Carine Robert, Laurent Delva, Nicole Balitrand, Sarolta Nahajevszky, Tamàs Masszi, Christine Chomienne, Béla Papp

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Hypereosinophilic syndrome (HES) has recently been recognized as a clonal leukemic lesion, which is due to a specific oncogenic event that generates hyperactive platelet-derived growth factor receptor-α-derived tyrosine kinase fusion proteins. In the present work, the effect of retinoids on the leukemic hypereosinophilia-derived EoL-1 cell line and on primary HES-derived cells has been investigated. We show that all-trans-retinoic acid (ATRA) inhibits eosinophil colony formation of HES-derived bone marrow cells and is a powerful inducer of apoptosis of the EoL-1 cell line. Apoptosis was shown in the nanomolar concentration range by phosphatidylserine externalization, proapoptotic shift of the Bcl-2/Bak ratio, drop in mitochondrial membrane potential, activation of caspases, and cellular morphology. Unlike in other ATRA-sensitive myeloid leukemia models, apoptosis was rapid and was not preceded by terminal cell differentiation. Use of isoform-selective synthetic retinoids indicated that retinoic acid receptor-α-dependent signaling is sufficient to induce apoptosis of EoL-1 cells. Our work shows that the scope of ATRA-induced apoptosis of malignancies may be wider within the myeloid lineage than thought previously, that the EoL-1 cell line constitutes a new and unique model for the study of ATRA-induced cell death, and that ATRA may have potential for the management of clonal HES.

Original languageEnglish
Pages (from-to)6336-6344
Number of pages9
JournalCancer Research
Volume66
Issue number12
DOIs
Publication statusPublished - Jun 15 2006

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Apoptosis induction by retinoids in eosinophilic leukemia cells: Implication of retinoic acid receptor-α signaling in all-trans-retinoic acid hypersensitivity'. Together they form a unique fingerprint.

  • Cite this