[Mechanism and clinical significance of anti-apoptotic gene bcl-2 expression in diffuse large B-cell lymphoma].

OBJECTIVE: To evaluate the molecular mechanism and prognostication of bcl-2 protein expression in different subgroups of diffuse large B-cell lymphoma(DLBCL) in Guangxi Zhuang Autonomous Region, China. METHODS: Immunohistochemical stains for CD10, bcl-6, MUM-1, bcl-2 and NF-κB were performed in 214 cases of DLBCL. The Hans immunologic classification was applied to classify DLBCL into GCB and non-GCB subgroups. Using a dual-probe fluorescence in-situ hybridization (FISH) assay, IgH/bcl-2 gene translocation and bcl-2 amplification were analyzed. RESULTS: In 214 cases of DLBCL, 30.8% (66/214) of cases were GCB and 69.2% (148/214) were non-GCB. Twenty-seven point three percent (18/66) of GCB subgroups and 59.5% (88/148) of non-GCB subgroups had bcl-2 protein expression, with a significant difference (P < 0.01). IgH/bcl-2 translocation was positive in 3.7% (8/214) of cases, even majority of them (6/8) was found in GCB subgroup, while represented only 9.1% of GCB case. There was a significant difference (P = 0.02) in bcl-2 gene amplification between GCB (27/66, 40.9%) and non-GCB subgroup (86/148, 58.1%). Among non-GCB cases, the expression of bcl-2 was correlated with that of NF-κB expression and bcl-2 gene amplification (r = 0.216 and 0.219, respectively, P < 0.05). No similar correlation was observed in GCB cases. The overall survival time of bcl-2-positive patients (31.4 ± 3.8) months was shorter than that of bcl-2-negative patients (40.2 ± 4.2) months. In conjunction with immunophenotypes and clinical stages, the bcl-2 positive patients had a 1.89 times higher risk than that of the bcl-2 negative patients. CONCLUSIONS: Majority of the cases were prognostically unfavorable non-GCB subgroups among DLBCL, which were characterized by high frequency of bcl-2 gene amplification and low frequency of IgH/bcl-2 translocation. The anti-apoptotic gene bcl-2 was frequently expressed in non-GCB subgroups and closely related to the gene amplification and NF-κB activation. bcl-2 positive patients had more short overall survival times, would face significant higher risk of death, these results suggested that bcl-2 could be a prognostic marker independent to clinical staging and immunophenotyping.

[Study on genetic aberrations of ocular mucosa-associated lymphoid tissue lymphomas occurring in southern China].

OBJECTIVE: To study the genetic aberrations of ocular extranodal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT) type occurring in patients from southern China. METHODS: Fifty seven paraffin-embedded ocular MALT lymphoma specimens from patients in southern China were studied by interphase fluorescence-in-situ hybridization (FISH) for genetic aberrations including t(11;18)(q21;q21)/API2-MALT1, t(1;14)(p22;q32)/IgH-bcl-10, t(14;18) (q32;q21)/IgH-MALT1 and bcl-6/FOXP1 gene translocations. RESULTS: Amongst the 57 cases studied, 9 cases (15.8%) showed chromosome translocations, including 4 cases (7.0%) of t(11;18)(q21;q21)/API2-MALT1, 1 case (1.8%) of t(14;18) (q32;q21)/IgH-MALT1, 1 case (1.8%) of bcl-6 gene-related chromosome translocation and 3 cases (5.3%) of IgH-unknown translocation partner. FISH revealed 17 cases (29.8%) with 3 copies of bcl-6 gene, 21 cases (36.8%) with 3 copies of MALT1 gene and 12 cases (21.1%) with 3 copies of both genes. CONCLUSIONS: The MALT lymphoma-associated chromosome translocations t(11;18)(q21;q21)/API2-MALT1 and t(14;18) (q32;q21)/IgH-MALT1 are demonstrated in ocular MALT lymphomas of southern Chinese patients. The prevalence is significantly different from that reported in northern Chinese and northern American patients, indicating a geographic heterogeneity in the MALT lymphoma-associated genetic aberrations. The presence of 3 copies of bcl-6 and MALT1 genes is the commonest genetic abnormalities observed in ocular MALT lymphomas, suggesting a possible role in MALT lymphomagenesis.

[A clinical study of chromosome translocations in extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue in Chinese patients].

OBJECTIVE: To investigate the genetic aberrations in extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) lymphomas from different sites of the body in Chinese patients. METHODS: Two hundred and seventeen paraffin-embedded MALT lymphoma specimens from 11 major sites were studied with interphase fluorescence in situ hybridization (FISH) to detect t (11; 18) (q21; q21)/API2-MALT1, t (1; 14) (p22; q32)/IGH-BCL10, (14; 18) (q32; q21)/IGH-MALT1 and BCL6 gene involved chromosome translocations. RESULTS: These translocations were mutually exclusive and detected in 21% (46/217) of the cases, including t (11; 18) (q21; q21) API2-MALT1 13% (29/217), t (1; 14) (p22; q32) IGH-BCL10 in 1% (3/217), t (14; 18) (q32; q21) IGH-MALT1 1% (2/217), BCL6 involved translocation in 2% (4/217) and IGH-unknown translocation partner in 4% (8/217). t (11; 18) (q21; q21) API2-MALT1 was found with the highest frequency in MALT lymphoma from lungs (47%, 8/17) and small intestine (29%, 4/14), followed by salivary gland (17%, 1/6), stomach (14%, 12/84) and ocular adnexae (6%, 4/68). t (1; 14) (p22; q32) was only detected in lungs (12%, 2/17) and stomach (1%, 1/84). t (14; 18) (q32; q21) was mainly detected in lungs (6%, 1/17) and ocular adnexae (2%, 1/68). BCL6 gene involved translocation was detected in salivary gland (17%, 1/6) and stomach (4%, 3/84). CONCLUSIONS: It is demonstrated that the four translocations occur with markedly variable frequencies in MALT lymphoma of different sites in Chinese patients. The distributions of these chromosome translocations in Chinese patients are slightly different from those reported in western patients.

Coulomb explosions and energy loss of molecular ions in plasmas.

Interactions of swift molecular ions with high-density plasma targets are studied by means of the linearized Vlasov-Poisson theory, allowing the dynamically screened interaction potential among the constituent ions to be expressed in terms of the classical plasma dielectric function. Coulomb explosions and the energy losses of a molecular ion are simulated by solving the equations of motion for the constituent ions. It is found that, due to the wakelike asymmetry of the interaction potential, the molecular axis tends to align itself along the beam direction. In addition, a strong enhancement of the energy loss of the molecular ion has been found in the initial stages of Coulomb explosions due to proximity of the constituent ions, but this effect diminishes at latter stages when the ions are sufficiently far apart.