A structurally abnormal breakpoint cluster region gene in a transcription factor, hLH-2-negative human leukemia cell line.
hLH-2, a transcription factor that contains double cysteine rich regions (LIM motifs) and a homeobox (Hox) DNA-binding domain shows aberrant high expression in all cases of chronic myelogenous leukemia (CML). This gene has been mapped to the chromosome 9q33-34.1, the same region as the reciprocal translocation that creates the breakpoint cluster region (BCR)-ABL chimera of the Philadelphia chromosome (Ph'). To investigate the possible involvement between the BCR-ABL fusion gene and hLH-2 in the pathogenesis of CML, an hLH-2-negative CML cell line, JK-1 that carries double Ph' chromosomes, was examined. Like other CML cells, high BCR-ABL fusion mRNA levels are expressed, but no transcript of hLH-2 was detected in JK-1 cells as determined by reverse transcriptase-polymerase chain reaction (RT-PCR). Compared with the CML cell line, K-562, an additional rearrangement of the BCR gene was observed in JK-1 as determined by Southern blot hybridization; however, the hLH-2 gene was normal. These findings raise interesting questions about the possible roles of either the abnormal BCR gene or other genetic events such as the complex chromosomal abnormalities that result in hLH-2 being turned off in JK-1 cells.
Wu
H K
HK
Ontario Cancer Institute, Department of Medicine, Faculty of Medicine, University of Toronto, Canada.
D001483:Base Sequence; D015139:Blotting, Southern; D002869:Chromosome Aberrations; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D015321:Gene Rearrangement; D005801:Genes, Homeobox; D018257:Helix-Loop-Helix Motifs; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics*; D008969:Molecular Sequence Data; D010677:Philadelphia Chromosome; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D016044:Fusion Proteins, bcr-abl