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Regulation of myeloblastin messenger RNA expression in myeloid leukemia
cells treated with all-trans retinoic acid
C Labbaye, J Zhang, JL Casanova, M Lanotte, J Teng, WH Miller and YE Cayre
Department of Physiology, Columbia University College of Physicians and
Surgeons, New York, NY 10032.
Retinoic acid is known to induce differentiation of human myeloid leukemia
cells in vitro. Recently, all-trans retinoic acid has been used to induce
remissions in patients with acute promyelocytic leukemia, probably through
differentiation of the leukemia cells. Myeloblastin (mbn) is a protease
that has been identified in the human leukemia cell line HL-60.
Downregulation of this protease can inhibit proliferation and induce
differentiation of HL-60-derived leukemia cells. Here we have investigated
the regulation of mbn messenger RNA (mRNA) expression in two human leukemia
cell lines, HL-60 and NB4, treated with all-trans retinoic acid. Under this
treatment, downregulation of mbn mRNA was observed in both cell lines, but
was considerably delayed in NB4 cells that carry the t(15;17) translocation
characteristic of acute promyelocytic leukemia. We have found that multiple
mechanisms were involved in the control of mbn mRNA expression. These
mechanisms were different in HL-60 and NB4 cells. Our results show that in
HL-60 cells, all-trans retinoic acid rapidly decreased transcription of
mbn. In contrast, in the t(15;17)-positive NB4 cells treated with all-trans
retinoic acid, upregulation of mbn mRNA expression was followed by a late
downregulation, both achieved via posttranscriptional mechanisms.
Volume 81,
Issue 2,
pp. 475-481,
01/15/1993
Copyright © 1993 by The American Society of Hematology
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