Increased expression of the c-myc gene may be related to the aggressive transformation of human myeloma cells.
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.
Nobuyoshi
M
M
Department of Internal Medicine, Hiroshima University, Japan.
Kawano
M
M
Tanaka
H
H
Ishikawa
H
H
Tanabe
O
O
Iwato
K
K
Asaoku
H
H
Sakai
A
A
Kuramoto
A
A
D015152:Blotting, Northern; D015139:Blotting, Southern; D002455:Cell Division / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology*; D015321:Gene Rearrangement / Q000502:physiology; D016259:Genes, myc / Q000502:physiology*; D006801:Humans; D009101:Multiple Myeloma / Q000235:genetics* / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D014407:Tumor Cells, Cultured / Q000473:pathology
D012333:RNA, Messenger; D012334:RNA, Neoplasm