Roles of translocation junction genes for proliferation and differentiation of hemotolymphoid cell

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The aim of the study is to identify genes that are involved in proliferation, differentiation and apoptosis for hematolymphoid cells and establish molecular markers useful for diagnosis and therapy. We have analyzed T-cell lymphoma breakpoint of chromosome 6q21 and identified TCBA1 (T-cell breakpoint cluster target 1). Its function on lymphomagenesis and cell differentiation remains to be explored. Mucosa-associated lymphoid tissue (MALT) lymphoma arises with chronic inflammation caused by H.pylori (gastric MALT lymphoma) or autoimmune diseases. Therefore, tumor cells are mixed with variable number of inflammatory cells.In an attempt to analyze heterogeneity of MALT lymphoma, we measured API2-MALT1 chimeric mRNA copy number by REAL-Time PCR and tumor cell ratio by IgVH genomic sequence. As a result, API2-MALT1 copy number per tumor cell was found to vary as much as 100 times among the patients. This indicates that the heterogeneity of MALT lymphoma may be reflected by the amount of tumor cell and also by API2-MLAT1 chimeric mRNA copy number. MALT lymphoma without API2-MALT1 chimeric mRNA is also an important disease category to be explored. We are applying Tissue FISH method to this problem. Function of the concogenic gene is an important issue. Retroviral vector is being used and in combination with stem cell transplantation, in vivo function of API2-MALT1 is being studied.