Expression of retinoic acid receptor-α mRNA in human leukemia cells with variable responsiveness to retinoic acid

R. E. Gallagher, F. Said, I. Pua, P. R. Papenhausen, E. Paietta, P. H. Wiernik

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

Retinoic acid receptor (RAR)-α mRNA expression was studied in a variety of myeloid leukemia cells with variable responsiveness to the induction of terminal differentiation by retinoic acid (RA). Cells from both the wild-type (wt), RA-responsive HL-60 promyelocytic leukemia cell line and a selected ≥300-fold RA-resistant subline expressed approximately equal amounts of two RAR-α transcripts, 4.0 and 3.1 kb in size. In wt cells, the RAR-α did not change during induction of granulocytic differentiation by RA or marcrophagic differentiation by 12-O-tetradecanoylphorbol-13-acetate (TPA). Relative to HL-60 cells, other cultured and fresh myeloid leukemia cells expressed 2.5-fold less to equal amounts of the RAR-α transcripts. The relative expression in six cases of acute promyelocytic leukemia (APL; two RA-responsive; one, previously treated with 13-cis-RA in vivo, equivocally RA-responsive) and one case of acute myelogenous leukemia (AML) with promyelocytosis (RA unresponsive) was 0.91 ± 0.14 versus 0.53 ± 0.14 for eight cases of nonpromyelocytic AML (p ≃ 0.001). Lymphoid leukemia cells expressed 2- to 5-fold less RAR-α mRNA. No qualitative variations in the mRNA transcripts were observed, although the 3.1 kb transcript was relatively decreased in three cases. The RAR-α gene was not amplified or detectably rearranged in any DNA source, although an apparent EcoRI restriction fragment length polymorphism was observed. It is concluded (a) that the steady-state level of RAR-α mRNA is not tightly correlated with natural responsiveness/unresponsiveness or, in some instances, acquired resistance to RA-induced differentiation and (b) that further studies are needed to determine if the mean 1.7-fold higher RAR-α mRNA level in APL cells could be an essential factor in the RA-responsiveness of APL cells, as primarily regulated at a different molecular level.

Original languageEnglish (US)
Pages (from-to)789-795
Number of pages7
JournalLeukemia
Volume3
Issue number11
StatePublished - Jan 1 1989

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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    Gallagher, R. E., Said, F., Pua, I., Papenhausen, P. R., Paietta, E., & Wiernik, P. H. (1989). Expression of retinoic acid receptor-α mRNA in human leukemia cells with variable responsiveness to retinoic acid. Leukemia, 3(11), 789-795.