Genomic organization of IgH gene compared with the expression of Bcl-2 gene in t(14;18)-positive lymphoma.
In three lymphoma cell lines carrying t(14;18), named FL-18, FL-218, and FL-318, the genomic organization of IgH gene was compared with the expression of bcl-2 gene; the t(14;18) of the FL-18 cells occurred downstream from the major breakpoint cluster region (mbr) of a bcl-2 gene, and that of the FL-218 and FL-318 cells within the mbr. The FL-318 expressed the normal-sized bcl-2 transcript of 8.5-kb mRNA having the noncoding region 3 to the mbr, which was found in the FL-18, and the FL-218 lacking the intact bcl-2 gene did not. This finding suggests that in t(14;18)-positive lymphoma having the breakpoint within the mbr, transcription of the nontranslocated bcl-2 allele is not necessarily silent. In addition, the FL-218 and FL-318 expressed aberrant bcl-2 transcripts and heterogenous IgH transcripts lacking the VH region, and the bcl-2 transcripts each comigrated with parts of the sterile IgH mRNAs. The FL-318, which did not exhibit switch recombination on either IgH allele, contained abundant amounts of l gamma mRNAs, a prerequisite for the recombination into the C gamma locus. One of the I-mRNA species comigrated with the aberrant bcl-2 transcript. The FL-18 and FL-218 lacking the I gamma mRNAs had completed switch recombination of both IgH alleles. This result raises a possibility that deregulated bcl-2 transcription caused by t(14;18) is capable of playing a role in class switch recombination of IgH gene.
Amakawa
R
R
Department of Internal Medicine, Faculty of Medicine, Kyoto University, Japan.
Fukuhara
S
S
Ohno
H
H
Matsuyama
F
F
Kato
I
I
Tanabe
S
S
Sideras
P
P
Mizuta
T R
TR
Honjo
T
T
Okuma
M
M
D015342:DNA Probes; D015245:Deoxyribonuclease BamHI; D015246:Deoxyribonuclease EcoRI; D015247:Deoxyribonuclease HindIII; D015252:Deoxyribonucleases, Type II Site-Specific; D015870:Gene Expression; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007621:Karyotyping; D008223:Lymphoma / Q000235:genetics*; D009693:Nucleic Acid Hybridization; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger / Q000378:metabolism; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D015342:DNA Probes; D007143:Immunoglobulin Heavy Chains; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D015245:Deoxyribonuclease BamHI; D015246:Deoxyribonuclease EcoRI; D015247:Deoxyribonuclease HindIII; C024408:endodeoxyribonuclease SacI; D015252:Deoxyribonucleases, Type II Site-Specific