High Frequency of BCL2 Translocation in Thai Patients with Follicular Lymphomas

ArticleinInternational Journal of Hematology 86(4):352-7 · December 2007with6 Reads
DOI: 10.1532/IJH97.A20709 · Source: PubMed
Abstract
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.
  • [Show abstract] [Hide abstract] 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.
    Article · May 2009
  • [Show abstract] [Hide abstract] 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.
    Article · Nov 2011
  • [Show abstract] [Hide abstract] ABSTRACT: Objective: Diffuse large B-cell lymphoma (DLBCL), as defined by 2008 World Health Organization (WHO) classification, is the most common subtype. Rituximab (R), a chimerical monoclonal antibody against the CD20 B-cell antigen, has shown improved outcomes in patients with newly diagnosed DLBCL. Based on clinical results, a retrospective analysis was performed of treatment outcome, using rituximab, in patients with DLBCL. Materials & Methods: Two hundred and twenty newly diagnosed patients with non-Hodgkin's lymphoma (NHL), between June 2001 and December 2006, were evaluated for histological subtypes and clinical characteristics. Ninety-nine patients with DLBCL were investigated further for clinical results after CHOP-like chemotherapy with or without rituximab. Results: Among 220 patients with NHL, 172 (78.2%) patients had B-cell lineage and 35 (15.9%) T/NK-cell lineage. Ninety-nine patients were diagnosed with DLBCL, which was the most common B-cell lineage subtype and accounted for 45% of the patients with NHL. Among the 99 patients with DLBCL, 43 received R-CHOP like chemotherapy (R-CHOP group), 29 received CHOP-like chemotherapy alone (CHOP group), 13 had other chemotherapy regimens, and 14 received supportive care only. The response rate was significantly higher in the R-CHOP group compared to the CHOP group (86% vs. 58.6%, p=0.012). The progression free survival was significantly higher in the R-CHOP group (p=0.05, HR=0.524, CI, 95%, 0.255-1.075). The survival benefit was also more favorable in the R-CHOP group (p=0.06, HR=0.520, CI, 95%, 0.253-1.067). Conclusions: DLBCL is the most common subtype of NHL. The addition of rituximab to CHOP-like chemotherapy increased the response rate and improved the therapeutic outcome with regard to the progression free survival. A longer follow-up duration is necessary to evaluate overall survival.
    Article · Oct 2012 · Molecular Medicine Reports
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