Analysis and use of bcl-2/IgH gene rearrangement in non- Hodgkin's lymphoma

Objective To elucidate the role and the significance of bcl 2 /IgH gene rearrangement in tumorigenesis, development and therapy of non Hodgkin’s lymphoma (NHL) Methods Polymerase chain reaction (PCR) can be used to detect bcl 2 gene rearrangement and serial dilution method can be used to define the sensitivity of PCR Nine kinds of malignant lymphoma cell lines (Su DHL 1, Su DHL 4, Su DHL 6, Su DHL 8, Su DHL 9, Su DHL 10, 8392, SB and Daudi dirived from B cell lymphoma were studied while 29 patients of NHL, including 11 cases of follicular NHL (F NHL), 11 cases of B cell diffuse NHL (D NHL) and 7 cases of T cell D NHL were studied Results Su DHL 4 and Su DHL 6 demonstrated bcl 2 (MBR)/IgH rearrangement, other cell lines had no rearrangement, all of cell lines did not present bcl 2(MCR)/IgH rearrangement In order to assess the sensitivity of PCR amplification, 1×10 7 cells from the Daudi cell lines without bcl 2/IgH rearrangement were admixed with serial 1/10 dilutions of cells from Su DHL 6 cell lines with bcl 2/IgH rearrangement, DNA was then extracted and amplified by PCR, it was demonstrated that the PCR product can be seen at a dilution of 1∶10 5, and one tumor cell with bcl 2/IgH rearrangement was detectable from 10 5 normal cells by PCR amplification Six of 22 cases of B cell lymphomas obtained a positive result, one of 7 cases of T cell lymphoma had rearrangement In 6 postitive results, 4 were detected in 11 cases of F NHL (36 4%), 2 in 11 cases of D NHL (18 2%) The bcl 2 gene breakpoint of 5 cases occurred in MBR, only one in MCR In 16 cases of untreated patients with F NHL, 4 cases demonstrated PCR positive cells both in bone marrow and peripheral blood All of bcl 2 gene breakpoints occurred in MBR When complete remission was obtained after chemotherapy, these breakpoints still existed Conclusion Bcl 2/IgH gene rearrangement are mainly associated with low grade B cell NHL The pattern of bcl 2 rearrangement is MBR IgH The detection of bcl 2 rearrangement by PCR provides a sensitive and specific assay of minimal residual diease (MRD) It helps to improve staging of disease, stratification and evalution of treatment