| Budget Amount *help |
¥3,790,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥390,000)
Fiscal Year 2007: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2006: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Research Abstract |
1. Long-Term Study of the Clinical Significance of Loss of Heterozygosity in Childhood Acute Lymphoblastic Leukemia Acute lymphoblastic leukemia (ALL) is one of the most common malignancies in childhood, with a widely variable outcome. Differences in the behavior and prognosis of the leukemia suggest that ALL can be divided into several biologic subgroups. We analyzed the loss of heterozygosity (LOH) of 6q, 9p, 11q, and 12p using 31 microsatellite sites to determine their overall frequency and clinical value. We have studied 244 primary ALL samples obtained from the Multicenter Trial ALL-BFM 90 of Childhood ALL group. These patients have now been followed clinically for over 8 years. LOH occured in 169 (69%) individuals in the following frequencies: 6q, 49 patients (20%); 9p, 97 patients (40%); 11q, 29 patients (12%); 12p, 60 patients (25%). Clinical data showed that those with 6q LOH were younger (p=0.01) and had lower WBC counts (P=0.02); patients with 9p LOH more frequently had CNS
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involvement (p=0.01) and T cell phenotype (p=0.0001); individuals with 11q LOH had a good response to induction chemotherapy (p=0.02); those with 12p LOH were younger(1)=0.005), frequently had precursor B ALL (p=0.001), and had a longer event-free survival (p=0.05). Taken together, these data confirm that LOH is a very frequent alteration in childhood ALL.
2. Aberrant Methylation in Promoter-associated CpG Islands of Multiple Genes in Acute Lymphoblastic Leukemia Methylation profile was analyzed in ten childhood acute lymphoblastic leukemia (ALL) and nine adult ALL cases. Four genes (p15, p16, RAR〓, FHIT) had methylation in both diseases, four genes (p14, Rb, MLH1, DAPK) showed no methylation in both diseases, and the two genes (APC, RIZ) demonstrated methylation only in adult ALL. Methylation of the RAR〓 was more frequent in adult ALL than childhood ALL (v0.01). The number of patients with methylation of multiple genes was higher in adult ALL than childhood ALL (p=0.006). Moreover, overall frequency of methylation was higher in adult ALL than childhood ALL (p=0.01). Less
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