| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Research Abstract |
1.Aberrant Methylation of Multiple Genes in Relapsed Childhood Acute Lymphoblastic Leukemia
Frequency of methylation in each gene was : MGMT,56%;RARβ,44%;and p16,22%, respectively. None of the p14,p15,Rb,APC,hMLH1,RIZ,DAPK, and FHIT genes were hypermethylated. Five (56%) of 9 cases showed methylation of at least one gene. All of the samples with hypermethylation in p16 and MGMT gene at relapse, had already acquired the change at the time of initial diagnosis. Interestingly, three of 4 cases with RARβ gene methylation at relapse did not have methylation of this gene at the time of initial presentation.
2.Methylation Analysis of the Adenomatous Polyposis Coli (APC) Gene in Adult T-Cell Leukemia/Lymphoma
APC methylation was found in 15 of 31 (48%) primary samples, and 2 of 4 (50%) ATL cell lines. Methylation of the APC gene occurred more frequently in acute ATL (12/21) (57%) than chronic ATL (1/8) (13%) (P=0.03). APC was not expressed in the APC-methylated ATL cell line ST1. Demethylation with 5-Azacytidine treatment restored APC expression in the ST1 cell line.
3.Methylation of the MLH1 Gene in Hematological Malignancies.
Aberrant methylation of the MLH1 gene was found in two of 31 (6 %) ATL patients, and in one of 12 (8 %) cell lines with MSI. MLH1 promoter was not methylated in either any of twelve peripheral blood samples from normal individuals or ALL samples. The MLH1 gene was expressed in the normal peripheral blood samples, but not in the MLH1-methylated cell line KCL22. Demethylation with 5-Azacytidine treatment restored MLH1 expression in the KCL22 cell line. Methylation of the MSH2 gene was not found in any of the samples.
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