| Budget Amount *help |
¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2002: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2001: ¥900,000 (Direct Cost: ¥900,000)
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| Research Abstract |
Several lines of evidence have shown that inactivation of tumor suppressor genes is closely associated with tumorigenesis in a wide variety of human tumors. Such inactivation is often caused by a mutation of one allele accompanied by loss of the second allele. To know genetic changes in blast crisis (BC) of chronic myelocytic leukemia (CML), we analyzed abnormalities of the SNF5 gene on long arm of chromosome 22 (22q). Cytogenetic analysis revealed abnormalities of chromosome 22 in 184 patients with hematologic neoplasms. All 122 patients with CML had t(9 ; 22)(q34 ; q11). Of the 122 patients, two had 22q- as well as t(9 ; 22)(q34 ; q11). One patient with myelodysplastic syndrome (MDS) showed -22 and 22q-, suggesting that both alleles of the SNF5 gene were deleted.
We examined 22q for allelic loss in the progression of CML, using microsatellite markers in 30 patients who progressed from chronic phase to BC. We detected loss of heterozygosity (LOH) on 22q in two of 18 patients with CML BC. We also examined allelic loss on 22q in 24 patients who progressed from MDS to acute myeloblastic leukemia (AML). Allelic loss was observed on 22q in one case of AML that had evolved from MDS.
In CML BC and other hematologic neoplasms showing 22 and 22q-, we performed PCR-SSCP analysis on the SNF5 gene to detect subtle mutations. We found mobility shifts inone case, however sequence analysis showed polymorphism.
Since one patient with MDS showed -22 and 22q-, FISH analysis on the SNF5 gene is now underway. Haplo in sufficiency may contribute to the progression of hematologic neoplasms including CML.
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