Defective c-myc and c-myb RNA turnover in acute myeloid leukemia cells.
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.
Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY 14263.
M R
MR
Baer
P
P
Augustinos
A J
AJ
Kinniburgh
D000328:Adult; D000368:Aged; D015152:Blotting, Northern; D003609:Dactinomycin / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016762:Genes, fos; D016259:Genes, myc; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics; D006207:Half-Life; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D020598:Proto-Oncogene Proteins c-myb; D012313:RNA / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects
D011518:Proto-Oncogene Proteins; D020598:Proto-Oncogene Proteins c-myb; D003609:Dactinomycin; D012313:RNA; D016178:Granulocyte-Macrophage Colony-Stimulating Factor