Colony-stimulating factor gene expression in human acute myeloblastic leukemia cells is posttranscriptionally regulated.
Normal human myeloid cells require certain colony stimulating factors (CSFs) for growth and differentiation. These CSFs are normally produced exogenously by accessory cells. However, human acute myeloid leukemia cells have been found, in certain instances, to have constitutive, endogenous production of one or more of these CSFs. In order to address the molecular basis of this apparently anomalous production of CSFs, we studied granulocyte-, monocyte-, and granulocyte/monocyte colony stimulating factor gene expression, gene structure, transcription rate, message stability, and message inducibility in human acute myeloid leukemia samples. CSF gene expression by Northern analysis was variable from no transcripts detectable to transcripts present for all three CSFs. No CSF gene structure abnormalities were detected by Southern blot analysis. Nuclear run-on assays found ongoing and relatively uniform CSF gene transcription irrespective of the levels of CSF expression detected by Northern analysis. However, the stability of the CSF transcripts appeared to correlate with the level detected on Northern blots. Despite the apparent similarity in the regulation of these CSFs to that seen in mature monocytes, the inducibility of the expression of these CSFs was found to differ significantly from that seen in these mature myeloid cells. Taken together, these results suggest that the expression of CSF genes in human myeloid leukemias is primarily mediated through posttranscriptional mechanisms. These mechanisms are separate for each of the CSFs and apparently different from that found in normal blood monocytes.
Ernst
T J
TJ
Department of Medicine, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115.
Ritchie
A R
AR
O'Rourke
R
R
Griffin
J D
JD
D015152:Blotting, Northern; D002467:Cell Nucleus / Q000502:physiology; D003115:Colony-Stimulating Factors / Q000235:genetics*; D003513:Cycloheximide / Q000494:pharmacology; D004273:DNA, Neoplasm / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D015321:Gene Rearrangement; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006133:Growth Substances / Q000235:genetics*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics*; D016173:Macrophage Colony-Stimulating Factor; D012323:RNA Processing, Post-Transcriptional / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects
D003115:Colony-Stimulating Factors; D004273:DNA, Neoplasm; D006133:Growth Substances; D012333:RNA, Messenger; D016179:Granulocyte Colony-Stimulating Factor; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003513:Cycloheximide; D013755:Tetradecanoylphorbol Acetate