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
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.

5 Reads
  • [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.
    International journal of hematology 05/2009; 89(3):326-31. DOI:10.1007/s12185-009-0259-8 · 1.92 Impact Factor
  • [Show abstract] [Hide abstract]
    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
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: We sought to investigate the role of the Bcl-2 translocation at the chromosomal and protein levels in minimal bone marrow (BM) infiltration by diffuse large B-cell lymphomas (DLBCL). Methods: The presence of the Bcl-2/IgH fusion gene was detected in BM samples and paraffin-embedded lymph node (LN) samples from 103 patients with DLBCLs using FISH. Bcl-2 protein levels in BM and paraffin-embedded tissues were quantified using immunocytochemistry (ICC) and immunohistochemistry (IHC), respectively. Results: Bcl-2/IgH translocation in paraffin-embedded LN tissue sections was observed in 43 (41.7%) patients by FISH. Of the 43 patients, the Bcl-2/IgH rearrangement in the bone marrow specimens occurred in 34 patients. The Bcl-2/IgH recombination rate in stage III cancers was not significantly different compared to the rate observed in stage I/II cancers (p = 0.101), respectively showing no statistical differences between stage IV and I/II (p = 0.179). In 64.7% (22/34) of the cases with t(14;18), Bcl-2 was detected based on ICC analysis. Positive Bcl-2 ICC staining and the t(14;18) translocation were positively correlated (p < 0.001). We then applied our FISH method to slides with at least one abnormal cell and were subjected to FISH analysis after staining. During the follow-up, no infiltration by cytomorphology for 16 DLBCL patients whose bone marrow presented Bcl-2/IgH gene rearrangement at diagnosis, and two cases were positive by morphology compared to FISH-positive results 6 months later; 9 out of 16 patients (56.3%) presented with positive Bcl-2/IgH results earlier than the morphology evaluation after 12 months. Conclusions: Utilizing both FISH and cytologic morphology, the assessment of Bcl-2/IgH translocation status could contribute to the better detection of minimal bone marrow infiltration and relapse receiving treatment by DLBCL cells.
    Clinical laboratory 07/2014; 60(6):989-98. DOI:10.7754/Clin.Lab.2013.130517 · 1.13 Impact Factor