Abrupt decrease of c-myc expression by antisense transcripts induces terminal differentiation and apoptosis in human promyelocytic leukemia HL-60 cells1
Recombinant plasmids containing v-myb' (803 bp fragment of the 3' end of v-myb) were constructed to induce sense or antisense v-myb' RNA expression with dexamethasone in human cells. These plasmids were used as a tool for the investigation of the role of c-myb gene in human leukemia cell proliferation and differentiation. They were transfected by electroporation into the K562 human leukemia cell line derived from a patient with chronic myelogenous leukemia in blastic crisis. After induction of transcription by dexamethasone, the plasmid with antisense v-myb' repressed the expression of p75c-myb from the endogenous c-myb gene of K562 cells. It also reduced the proliferation rate of K562 cells to 50% of the control level, and induced these K562 cells to express the myelomonocytic differentiation cell surface marker CD13 and increased NBT reducing activity. The plasmid with sense v-myb' did not have an effect on p75c-myb expression, the proliferation of K562 cells or the expression of myelomonocytic differentiation phenotypes. These observations suggest that antisense v-myb' RNA represses p75c-myb expression and that a decrease of p75c-myb suppresses K562 cell proliferation and induces its differentiation towards the myelomonocytic lineage.