Transcription of hematopoietic-associated oncogenes in childhood leukemia.

Abstract

We have examined the transcriptional expression of the cellular homologues of several retrovirus-associated oncogenes, myc, rel, rasH, myb, src, and erb, in uncultured childhood leukemia and normal hematopoietic cells, as a first step in determining their normal function and possible association with human neoplasia. Cellular myc-specific RNA was detected in all 30 samples of hematopoietic tissue examined, including 18 leukemias of both the lymphoid and myeloid series, three lymphomas, five normal leukocytes, and four cell lines. Although the level of expression varied over a 25-fold range, no general pattern based on cell type or disease state was evident. In addition, in all cell types examined, a single-molecular-weight myc-specific RNA species was observed. Transcriptional expression of the rel and rasH genes showed a similar lack of specificity, with the rasH gene being expressed at a low uniform level in all cell types examined. myb expression was marginally detectable in most samples, although the myeloid leukemia cells possessed approximately 4-fold higher levels. The expression of src was relatively low in most samples, with markedly elevated levels in a few diverse leukemia samples. erb expression was undetectable in all but two acute myelogenous leukemia samples. Analysis of one patient who had high levels of myc, erb, and src expression before therapy revealed a dramatic reduction in erb and src expression but not myc expression while the patient was in remission. These results indicate that primary human leukemia cells, as well as normal leukocytes, do express the cell homologues to several retrovirus-associated oncogenes, that some leukemia cells express high levels of several oncogenes, and that some of these genes are differentially expressed in specific subpopulations of cells.