|Budget Amount *help
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2003: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2002: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2001: ¥1,500,000 (Direct Cost: ¥1,500,000)
Indolent B-cell malignancy (IBM) occasionally undergo high-grade transformation (HT), a phenomenon in which IBM cells become larger cells. This research project aimed at profiling of gene expression involved in the HT mechanism of IBM. The following results were yielded.
1.In a HT case of splenic marginal zone B-cell lymphoma, a subtype of IBM, we found increased expression of plasmacytic markers such as MUM (multiple myeloma oncogene)1, CD138, and fibroblast growth factor receptor (FGFR)-3 frequently overexpressed by plasmacytoma, as compared with those before HT. It was suggested that the molecular basis of HT was associated with plasmacytic differentiation. Overexpression of FGFR3 was also seen in a case of peripheral T-cell lymphoma. An immunohistochemical study on diffuse large B-cell lymphomas (DLBCL) showed plasmacytom-like co-expression of FGFR3 and CD138 in some cases. Nuclear immunoreactivity of FGFR3 was observed in CD138 -negative DLBCL, suggesting that FGFR3 was phosphorylated, as a tyrosin-kinase, and transferred into nucleus.
2.Follicular lymphomas are known to frequently undergo HT. We found that FLs negative for CDlO and/or BCL6 frequently expressed MUM1, and tended to proliferate in a diffuse fashion. Expression patterns of CD10, BCL6, and MUM1 did not change before and after recurrence in some FLs without HT. FL cells however, rarely expressed FGFR3 and CD138. A small-scale study on FL using comparative genomic hybridization (CGH) technique did not show significant difference of chromosomal amplification between MUM1-postive and negative cases.
In conclusion, the heterogeneity of molecular basis was suggested in HT of IBM.