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 regio ns (LIM motifs) and a homeobox (Hox) DNA-binding domain shows aberrant high expression in all cases of chronic myelogenous leukemia (CML). T his gene has been mapped to the chromosome 9q33-34.1, the same region as the reciprocal translocation that creates the breakpoint cluster re gion (BCR)-ABL chimera of the Philadelphia chromosome (Ph'). To invest igate 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 t hat 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 transcriptas e-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 ge ne was normal. These findings raise interesting questions about the po ssible roles of either the abnormal BCR gene or other genetic events s uch as the complex chromosomal abnormalities that result in hLH-2 bein g turned off in JK-1 cells.