| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2004: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2003: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Research Abstract |
Anaplastic large cell lymphoma(ALCL) is a subtype of non-Hodgkin's lymphoma, which is characterized by a peculiar histology and a cytogenetic abnormality of t(2;5). As a consequence of t(2;5), the ALK gene on chromosome 2q23 and the NPM gene on 5q35 fuse to produce a chimeric protein NPM-ALK. These cases are positive for ALK immunohistochemistry, and account for approximately 70% of ALK-positive ALCL, and show nuclear ALK staining. ALK is translocated to other genes in the rest of 30% of the cases, which show cytoplasmic ALK staining. NPM-ALK translocation has recently been well investigated as a model of lymphomagenesis, but the variant ALK translocation is poorly understood. Therefore, the present study aimed to characterize the variant ALK translocation. First of all, presence of variant ALK translocation in cell lines was screened. Reverse transcriptase-inediated polymerase chain reaction(RT-PCR) for ALK tyrosine kinase domain was performed for 15 cell lines of ALCL or T-cell lymphoma. In addition to SUDHL-1 and Karpas299,which are known to have NPM-ALK,3 lines, AST-1,DL-40 and DL-110 were positive. However, NPM-ALK and other reported variant ALK translocations were absent for all these 3 cell lines. ALK immunohistochemistry and Western blotting were also negative, and Northern blotting showed very low level of ALK expression. The ALK expression has not been documented in normal hematolymphoid cells, but the low expression without translocations was recognized in this study for the first time. Next, the variant ALK translocation was examined for clinical samples, and was recognized in 6 cases. ALK was transfused to ATIC in 3 cases, TPM3 in 2,and TFG in 1. For one case, the translocation partner could not be identified. To date, TPM3 has been reported as the most frequent partner for ALK in the Western countries, but this study show that ATIC is frequent for Japanese patients.
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