Increased expression of the c‐myc gene may be related to the aggressive transformation of human myeloma cells

Summary. Alteration and abnormal expression of the c‐myc oncogene were investigated in human multiple myeloma. Human myeloma cells were highly purified (more than 95%) from bone marrow aspirates in 14 cases of advanced multiple myelomas and one case of plasma cell leukaemia. Southern blotting revealed that a rearranged configuration of c‐myc gene was found in only one case of them, but this was a novel truncation of the gene in its coding exon II: a rearranged 3·4 kb band was detected by digestion with Xba I using c‐myc exon II probe, but no rearranged band was found using exon III probe. In this case, the truncated c‐myc allele was not transcribed: normal sized (2·4 kb) c‐myc mRNA was markedly expressed, but no aberrant mRNA was detected. On the other hand, by Northern blotting, the nine cases, including the case with the rearranged c‐myc gene, showed increased expression of normal sized (2·4 kb) c‐myc mRNA. Elevated c‐myc mRNA expressions were well related to the in vitro proliferation (³H‐TdR uptake), but not to IL‐6 response. Interestingly, extremely high expressions of c‐myc mRNA were detected in two cases of aggressive myelomas, including the case with the rearranged c‐myc gene, and in one of plasma cell leukaemia. These two cases of aggressive myelomas were the ones who showed the markedly high ³H‐TdR uptakes, and had the common clinical features with the formation of an extramedullary mass and very short survival. These results suggest that the activation of c‐myc gene could induce high proliferative activities and the subsequent aggressive transformation of myeloma cells.