Defective c-myc and c-myb RNA turnover in acute myeloid leukemia cells
MR Baer, P Augustinos and AJ Kinniburgh
Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY 14263.
Dysregulated expression of the c-myc and c-myb protooncogenes has been
implicated in the pathogenesis of acute myeloid leukemia (AML). To
elucidate mechanisms of c-myc dysregulation in AML cells, we studied c- myc
RNA turnover in peripheral blood blasts from eight patients using
actinomycin D transcription blockade. Rapid c-myc RNA turnover was seen in
cells from six patients, with half-lives of approximately 30 minutes,
similar to those reported in normal myeloid cells, in HL-60 cells, and in
other cell lines. c-myc RNA turnover was prolonged in cells of the other
two patients, with half-lives of greater than 75 minutes. c-fos RNA
turnover was rapid in blasts from all eight patients, with half-lives of
approximately 15 minutes. Stabilization of GM-CSF transcripts was not
observed. In contrast, c-myb RNA half-lives were greater than 75 minutes in
cells of the two patients with prolonged c-myc RNA turnover, as compared to
30 minutes in cells of the other six patients. Enhanced stability of both
c-myc and c-myb RNA species suggests that a defect exists in a trans-acting
factor that destabilizes both of these normally labile RNAs. Incomplete
correlation between c-myc RNA levels and half-lives indicates regulation of
c-myc expression at the level of transcription or nuclear transport in
addition to posttranscriptional regulation.
Volume 79,
Issue 5,
pp. 1319-1326,
03/01/1992
Copyright © 1992 by The American Society of Hematology
