Study Of Microsatellite Instability And Loss Of Heterozygosity On Chromosome 8 In Leukemia

[Objective] To study the function of microsatellite instability (MSI) and loss of heterozygosity (LOH) on chromosome 8 during the pathogenesis of acute leukemia and to investigate the significance of MSI and LOH in detecting the minimal deletions of chromosome. [Methods] MSI and LOH in 51 cases of leukemia, including 40 cases of acute leukemia (AL) and 11 cases of chronic leukemia (CL), and 7 cases of myelodysplastic syndrome (MDS) were detected by PCR amplification at 4 microsatellites on chromosome 8, gel electrophoresis and argentine dye. [Results] 11 cases of leukemia demonstrated LOH and/or MSI at one or more loci. LOH was found in 2 cases (2/40) of AL at D8S511 and D8S258 on 8P22 respectively. LOH was observed in 5 cases (5/22) of acute myeloblastic leukemia (AML) at D8S559 on 8q22; in 7 cases (7/22) of AML and one case (1/18) of acute lymphocytic leukemia (ALL) at D8S555 on 8q22 respectively. The frequencies of LOH at D8S559 and D8S555 in AML were 22.7% and 31.8%, which were significantly higher than that of in ALL (0% and 5.6%) (p=0.040 and p=0.044, p<0.05). Furthermore, among the cases of AML showed LOH, 71.4% (5/7) demonstrated LOH at multi-locus. None of 11 cases of CL and 7 cases of MDS showed LOH at these 4 loci. MSI was observed only in 3 cases of leukemia (3/51) and 1 case of MDS. [Conclusions] AML showed significantly higher LOH frequencies than ALL on 8p22, which suggest that there may be some gene alterations related to AML. Microsatellite alterations of multi-locus observed in leukemia indicate that thepathogenesis and progress of leukemia is related to the multi-ragion and multi-step changes of chromosomes.