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, Elisabeth M. Paietta, P. H. Wiernik

Research output: Contribution to journalArticle

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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 - 1989

Fingerprint

Retinoic Acid Receptors
Tretinoin
Leukemia
Messenger RNA
Myeloid Leukemia
Myeloid Cells
Acute Myeloid Leukemia
Lymphoid Leukemia
Isotretinoin
Acute Promyelocytic Leukemia
HL-60 Cells
Tetradecanoylphorbol Acetate
Restriction Fragment Length Polymorphisms
Lymphocytes
Cell Line
DNA

ASJC Scopus subject areas

  • Cancer Research
  • Hematology

Cite this

Gallagher, R. E., Said, F., Pua, I., Papenhausen, P. R., Paietta, E. M., & 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.

Expression of retinoic acid receptor-α mRNA in human leukemia cells with variable responsiveness to retinoic acid. / Gallagher, R. E.; Said, F.; Pua, I.; Papenhausen, P. R.; Paietta, Elisabeth M.; Wiernik, P. H.

In: Leukemia, Vol. 3, No. 11, 1989, p. 789-795.

Research output: Contribution to journalArticle

Gallagher, RE, Said, F, Pua, I, Papenhausen, PR, Paietta, EM & Wiernik, PH 1989, 'Expression of retinoic acid receptor-α mRNA in human leukemia cells with variable responsiveness to retinoic acid', Leukemia, vol. 3, no. 11, pp. 789-795.
Gallagher, R. E. ; Said, F. ; Pua, I. ; Papenhausen, P. R. ; Paietta, Elisabeth M. ; Wiernik, P. H. / Expression of retinoic acid receptor-α mRNA in human leukemia cells with variable responsiveness to retinoic acid. In: Leukemia. 1989 ; Vol. 3, No. 11. pp. 789-795.
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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.",
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AU - Said, F.

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