High Frequency of BCL2 Translocation in Thai Patients with Follicular Lymphomas
Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.International Journal of Hematology (Impact Factor: 1.92). 12/2007; 86(4):352-7. DOI: 10.1532/IJH97.A20709
Follicular lymphoma is characterized by chromosomal translocation involving BCL2 and immunoglobulin heavy chain genes (IgH). That the incidence of follicular lymphoma and the previously reported frequency of BCL2 translocation are lower in Asians than in Caucasians implies a different molecular pathology. The study of BCL2 rearrangement will yield deeper insights into the pathogenesis of follicular lymphomas and into clinical applications of molecular diagnosis for Asian follicular lymphoma patients. BCL2 /IgH translocation was analyzed in paraffin-embedded tissues from follicular lymphoma patients by using polymerase chain reaction (PCR) analysis of the major breakpoint region (MBR), the intermediate cluster region (ICR), and the minor cluster region. In addition, fluorescence in situ hybridization (FISH) analysis with split-signal BCL2 probes was performed. PCR analysis revealed BCL2 rearrangement in 12 (23.5%) of 51 cases (10 MBR and 2 ICR breakpoints). This frequency is lower than the frequencies reported from Western countries (40%-60%). DNA sequencing of the breakpoints revealed nucleotide insertions suggesting V(D)J recombination-mediated mechanisms. On the other hand, FISH analysis revealed 11 (84.6%) of 13 cases with positive signals for BCL2 translocation. Our results suggest that BCL2 translocation is essential for the pathogenesis of follicular lymphoma in Thai patients. In addition, the data demonstrate the low sensitivity of the PCR for diagnostic testing and suggest that split-signal FISH is the method of choice.
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ABSTRACT: We conducted a retrospective analysis to evaluate the impact on clinical outcomes of adding rituximab to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) treatment for diffuse large B-cell lymphoma (DLBCL) patients in Japan. A propensity score method was used to compensate for the non-randomized study design. From January 2000 to December 2004, 378 patients who were newly diagnosed with DLBCL at 13 institutes were enrolled: 123 in the rituximab plus CHOP-based chemotherapy (R+) group, and 255 in the CHOP-based chemotherapy only (R-) group. The complete response rate was significantly higher in the R+ group than in the R- group (77.7 vs. 69.4%, P < 0.001). The progression-free survival (PFS) at 2 years was 62.4% in the R+ group and 57.0% in the R- group. The 2-year overall survival (OS) was 76.9% for the R+ group and 70.5% for the R- group. A multivariate analysis revealed that the addition of rituximab was a strong independent prognostic factor for PFS (hazard ratio 0.64, 95% CI 0.43-0.96, P = 0.031). A subgroup analysis revealed that R+ particularly benefited younger patients (hazard ratio 0.25, 95% CI 0.08-0.75, P = 0.013). IPI also showed significant impact for PFS (hazard ratio 1.82, 95% CI 1.55-2.14 for one score increase, P < 0.001) as well as OS (hazard ratio 2.10, 95% CI 1.71-2.57, P < 0.001). In summary, the addition of rituximab to CHOP-based chemotherapy results in better outcomes for Japanese DLBCL patients, particularly younger patients.International journal of hematology 05/2009; 89(3):326-31. DOI:10.1007/s12185-009-0259-8 · 1.92 Impact Factor
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ABSTRACT: The purpose of this study was to investigate the roles of bcl-2 chromosomal translocation and Bcl-2 protein expression in follicular lymphoma (FL) minimal bone marrow (BM) infiltration. We identified the same bcl-2/IgH fusion gene in paraffin-embedded lymph node (LN) samples and BM samples using immunohistochemistry (IHC), immunocytochemistry (ICC), cytologic morphology and fluorescence in situ hybridization (FISH). The presence of the Bcl-2/IgH fusion gene in the BM samples and paraffin-embedded LN samples from 56 patients with follicular lymphomas was detected using FISH. The Bcl-2 protein levels in BM and paraffin-embedded tissues were quantified using ICC and IHC, respectively. Approximately 78.6% (44/56) of the paraffin‑embedded LN tissue sections that underwent FISH analysis had a bcl-2/IgH translocation. The primary lesion was also positive for the bcl-2/IgH fusion gene, as were the BM minimal infiltrates. The bcl-2/IgH rearrangement occurred in 88.6% (39/44) of the BM specimens. The bcl-2/IgH recombination rate in stage III/IV cancers was significantly different to that observed in stage I/II cancers (p=0.041). In 59% (23/39) of the cases with t(14;18), Bcl-2 was found to be present as assessed by ICC. Positive Bcl-2 ICC staining and the t(14;18) translocation (as detected using FISH) were positively correlated (p=0.028). We then applied the FISH method to slides that had previously been morphologically evaluated using Wright-Giemsa staining; any slides with at least one abnormal cell were subjected to FISH analysis following staining. The assessment of bcl-2/IgH translocation status may contribute to the better detection of minimal BM infiltration by FL cells. Utilizing FISH and cytologic morphology techniques allows for earlier and more accessible BM examination.Molecular Medicine Reports 11/2011; 5(2):383-7. DOI:10.3892/mmr.2011.663 · 1.55 Impact Factor
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ABSTRACT: Aims: To investigate t(14;18)/IGH-BCL2 in follicular lymphoma (FL) cases from Taiwan. Methods and results: We retrospectively studied 93 consecutive cases, using immunohistochemistry and fluorescence in-situ hybridization (FISH). Fifty-nine (63%) tumours were low-grade (LG) and 34 (37%) were high-grade (HG; 24% FL3A and 13% FL3B). FISH showed IGH, BCL2 and BCL6 rearrangements in 59%, 47% and 11% of cases, respectively, and MYC rearrangement in 5% of FL3A tumours and 25% of FL3B tumours. The translocation partner of all BCL2 rearrangements was IGH, with IGH-BCL2 fusion in 63% of LG tumours and 18% of HG tumours. LG tumours were enriched with a CD10+/bcl-2+/MUM1- phenotype, and were frequently associated with BCL2 rearrangement but less commonly with BCL6 rearrangement. FL3A tumours were more closely related to FL3B tumours than to LG tumours in immunophenotype and genetic aberrations. There was no statistically significant difference between grade 1 and two tumours, between FL3A and FL3B tumours or between nodal and extranodal tumours in immunophenotypic or FISH findings. The cumulative survival rate was higher in LG FL patients with IGH-BCL2 translocation than in those without rearrangement. Conclusions: In Taiwan, FL3A tumours were more closely related to FL3B tumours than to LG tumours, and a literature review showed that the frequency of t(14;18)/IGH-BCL2 in FL in Taiwan is among the lowest in the world.Histopathology 02/2013; 63(1). DOI:10.1111/his.12119 · 3.45 Impact Factor
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