The Correlated Study Of Microsatellite Instability And Loss Of Heterozygosity Of TEL Gene In Childhood Acute Lymphoblastic Leukemia

Object We carry out a study on microsatellite instability ( MSI) and loss of heterozygosity ( LOH )of the 4 sites linked to TEL gene on chromosome 12, in order to find out the correlation between MSI, LOH of TEL gene and the occurrence, progression of children acute lymphoblastic leukemia ( ALL) .Method MSI and LOH in 53 cases of children ALL, 23 cases of adult acute myeloblastic leukemia (AML) , 21 cases of adult ALL, 5 cases of normal children and 15 cases of benign hematopathies were detected by multiplex-PCR amplification at 4 microsatellites linked to TEL gene on chromosome 12, gel electrophoresis and argentine dye.Result we detected LOH in 23 cases out of 53 children ALL, the frequency of LOH on 4 microsatellites ( D12s89, D12s98, D12s269, D12s358 ) was 43.40% (23/53), among those microsatellites, the expression ratio of LOH on D12s89 was the highest 39.62%(21/53). There was only one case detected MSI on D12s89, D12s98, D12s269 respectively, its frequency was 3.77% ( 2/53 ) . At the same time, LOH and MSI were observed in the three stages (beginning, relapse, remission ) of 13 cases of childhood ALL patients, the frequency of LOH in the three stages was 38.46%, 15.38 and 46.15% respectively. One case of childhood ALL was not found LOH and MSI in the beginning stage, but in the relapse stage LOH was found in 3 loci. Two cases of childhood ALL, LOH were consistently detected in the three stages. The frequencies of LOH and MSI on those four sites in 23 AML are all 8.69% (2/23 ). We find 9.52% ( 2/21) and 14.29 ( 3/21 )cases in 21 adult ALLs expressed LOH and MSI respectively. The frequency of LOH on 3 loci (D12s89, D12s98, D12s358) in childhood ALL was higher than that of adult AML and ALL at the time of diagnosis (x~2 =4.581 ~ 9.703, p<0.05). None of 5 healthy children and 15 cases of benign hematopathies showed LOH and MSI on these 4 loci.Conclusion since we get a high frequency of LOH on the loci linked to TEL gene on chromosome 12, the mutation of the TEL gene play an important role in the initiation and the development of childhood ALL. Our finding of LOH and MSI in several sites at the same time means that childhood ALL is an accumulate result from a multi-sites/steps mutation of TEL gene. The detection of microsatellite instability is a useful cytogenetic marker for the study of pathogenesis, screening and locating anti-oncogene in malignant hematopathies, it takes an...