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, T. Masszi, Christine Chomienne, Béla Papp

Research output: Article

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 - jún. 15 2006

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Hypereosinophilic Syndrome
Retinoic Acid Receptors
Retinoids
Tretinoin
Hypersensitivity
Apoptosis
Cell Line
Myeloid Leukemia
Mitochondrial Membrane Potential
Phosphatidylserines
Caspases
Eosinophils
Bone Marrow Cells
Cell Differentiation
Protein Isoforms
Cell Death
Neoplasms
Proteins

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Apoptosis induction by retinoids in eosinophilic leukemia cells : Implication of retinoic acid receptor-α signaling in all-trans-retinoic acid hypersensitivity. / Robert, Carine; Delva, Laurent; Balitrand, Nicole; Nahajevszky, Sarolta; Masszi, T.; Chomienne, Christine; Papp, Béla.

In: Cancer Research, Vol. 66, No. 12, 15.06.2006, p. 6336-6344.

Research output: Article

Robert, Carine ; Delva, Laurent ; Balitrand, Nicole ; Nahajevszky, Sarolta ; Masszi, T. ; Chomienne, Christine ; Papp, Béla. / Apoptosis induction by retinoids in eosinophilic leukemia cells : Implication of retinoic acid receptor-α signaling in all-trans-retinoic acid hypersensitivity. In: Cancer Research. 2006 ; Vol. 66, No. 12. pp. 6336-6344.
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