Alteration in the cellular response to retinoic acid of a human acute promyelocytic leukemia cell line, UF-1, carrying a patient-derived mutant PML-RARα chimeric gene

Atsushi Sato, Masue Imaizumi, Yoshiyuki Hoshi, Takeshi Rikiishi, Kunihiro Fujii, Masahiro Kizaki, Hiroyuki Kagechika, Akira Kakizuka, Yutaka Hayashi, Kazuie Iinuma

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Cellular response to all-trans retinoic acid (ATRA) of acute promyelocytic leukemia (APL) with patient-derived mutant PML-retinoic acid receptor-α (PML-RARα) was investigated using an APL cell line, UF-1, carrying Arg611Trp mutation in PML-RARα. Although the mutant protein showed a decreased ligand-dependent transcriptional activity and retained a dominant-negative effect on normal RARα, UF-1 cells underwent growth inhibition, maturation and apoptosis in response to ATRA at 1 μM, but not ≤100 nM, after 4 days of treatment with ATRA. Moreover, in the presence of 1 μM ATRA, approximately 50% of UF-1 cells expressing annexin V, an early-apoptotic marker, was negative for CD11b and showed immature morphology. These findings suggest that UF-1 cells, despite expressing mutant PML-RARα protein, can be induced by ATRA to undergo differentiation and apoptosis through RA-inducible mechanism(s), in which a proportion of apoptosis may occur independent of terminal differentiation. This unique cell line may be useful for investigating the pathogenesis of ATRA resistance and the mechanism of ATRA-induced apoptosis in APL.

Original languageEnglish
Pages (from-to)959-967
Number of pages9
JournalLeukemia Research
Volume28
Issue number9
DOIs
Publication statusPublished - 2004 Sep 1

Keywords

  • 9-cis-retinoic acid
  • 9CRA
  • APL
  • ATRA
  • Acute promyelocytic leukemia
  • Apoptosis
  • Differentiation
  • PML-RARα
  • PML-retinoic acid receptor-α
  • RXR
  • Retinoic acid
  • acute promyelocytic leukemia
  • all-trans retinoic acid
  • retinoid X receptor

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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