| Co-Investigator(Kenkyū-buntansha) |
NAKAMURA Shigeo AICHI CANCER CENTER,RESEARCH INSTITUTE, RESEARCHER, 研究所, 研究員 (80180363)
KAGAMI Yoshitoyo AICHI CANCER CENTER,RESEARCH INSTITUTE, RESEARCHER, 研究所, 研究員 (30270721)
JOH Tatsuro AICHI CANCER CENTER,LAB.OF CHEMOTHERAPY, RESEARCHER, 化学療法部, 研究員 (70280807)
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| Research Abstract |
A specific chromosome translocation is recurrently found in a specific type of hematologic malignancy and the translocation junction region genes have been recognized to play and important role in hematopoietic cell differentiation and proliferation. Our research for three years produced following results.
1. MLL gene associated with infantile leukemia and therapy-related leukemia
We produced the specific antibody against N-terminal MLL recombinant protein and showed that the MLL product is localized in nuclei. We also showed that the MLL-partner chimeric products localize in nuclei irrespective of translocation partner genes. We succeeded in establishing leukemia cell lines which can express MLL-LTG9 chimeric product, the most common type of therapy-related leukemia, upon IPTG induction. Using this system, we demonstrated that Hox-a7, b7, c9 are the target for chimeric MLL products.
2. BCLl/cyclin Dl gene on 11q13 chromosome translocation junction region :
We established the specific mono
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clonal antibody, 5D4, which can immuno-stan formalin-fixed, paraffin-embedded tissues. Importantly, we have shown that the positive staining reflected overexpression of cyclin Dl. We have examined 151 cases of mantle cell lymphoma (MCL) and found that 85% showed positive staining. Furthermore, the negative group of MCL has been shown to be a group with good prognosis distinct from the positive group of MCL, indicating the immunostaining is very important in selecting therapy strategy.
3. Diffuse large B-cell lymphoma (DLBL) and mucosa-associated lymphoid tissue (MALI) lymphoma :
DLBL constitutes of heterogeneous subtypes of B-cell lymphoma. We could identify three groups based on immunophenotype. Major translocation junction genes in B-cell lymphoma development are BCLl, BCL2, and BCL6, but gene rearrangement of these genes failed to identify any unique subtypes. MALT lymphoma has similar immunophenotype with DLBL, and we are trying to disclose 18q2 1 translocation junction genes which also should be useful in dissecting DLBL. Less
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