Genetic and epigenetic factors involved in B‐cell lymphomagenesis

Seto, Masao

doi:10.1111/j.1349-7006.2004.tb03249.x

Cited by 27 publications

(21 citation statements)

References 36 publications

(62 reference statements)

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“…However, Bcl2 translocation alone is not sufficient for cells to become malignant, the multigenetic (also epigenetic) alterations are likely to be required for FL development. 14 Our results indicate that the other FL cases express four types of genetic alterations involved in the pathogenesis, that is, Bcl2 translocation, Bcl6 translocation, Bcl2 amplification and other unknown gene alterations. Bcl2 translocation can only explain part of the pathogenesis of this type of FL.…”

Section: Discussionmentioning

confidence: 93%

“…Aberrant Bcl2 expression prevents cell death of FL cells originating from follicular centre cells, while at the same time follicular dendritic cells provide them with growth signals. 14 However, in FL without the t(14;18) translocation, Bcl6 rearrangement is considered to play an important role. 9 Some evidence indicates that Bcl6 may function to protect cells against terminal differentiation, and that differentiation block can be oncogenic.…”

Section: Introductionmentioning

confidence: 99%

“…9 Some evidence indicates that Bcl6 may function to protect cells against terminal differentiation, and that differentiation block can be oncogenic. 14,15 However, the relationship between Bcl6 rearrangement and its expression is uncertain. How this translocation influences the pathogenesis of FL is still unknown.…”

Section: Introductionmentioning

confidence: 99%

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Low-grade follicular lymphoma with t(14;18) presents a homogeneous disease entity otherwise the rest comprises minor groups of heterogeneous disease entities with Bcl2 amplification, Bcl6 translocation or other gene aberrances

et al. 2005

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JapanFollicular lymphomas (FL) are morphologically classified into grades 1, 2, 3a and 3b by the World Health Organization. Bcl2, Bcl6 and CD10 are phenotypic markers of FL while the Bcl2 t(14;18) and Bcl6 t(3q27) gene translocations are common genetic changes. However, to date, there has been no integrated analysis based on phenotype, grade and genotype from large numbers of FL cases. We graded 261 cases of FL and determined their phenotypes and gene alterations. According to the antigen markers and gene alterations of 147 cases, we classified FL into typical and the others types. The typical group, which includes 69% cases of FL, is characterized by low histological grade (grade 1, 2), coexpression of BCL2 and CD10 and Bcl2 gene translocation. The rest comprises a small part of low-grade FL without Bcl2 gene translocation and high-grade (grade 3a, 3b) FL. These FLs include some heterogeneous disease entities. They are characterized by high histological grade (87%), no definite expression of BCL2 or CD10 and several kinds of gene aberrances including Bcl2 translocation, Bcl6 translocation, Bcl2 amplification or other unknown gene abnormality. Our findings indicate that typical FL presents a homogeneous disease entity whereas the rest comprises heterogeneous diseases entities.

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Section: Discussionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

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Low-grade follicular lymphoma with t(14;18) presents a homogeneous disease entity otherwise the rest comprises minor groups of heterogeneous disease entities with Bcl2 amplification, Bcl6 translocation or other gene aberrances

et al. 2005

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“…Thus, the pathological status of t(14;18) translocation is the overexpression of the Bcl2 protein in the GC, resulting from an error in transcriptional control. 2 …”

Section: Bcl2 Genementioning

confidence: 99%

BCL2 and MYC Dual-Hit Lymphoma/Leukemia

Tomita

2011

J Clin Exp Hematopathol

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Translocation of the BCL2 gene on the chromosome band 18q21.3 results in consistent expression of the Bcl2 protein, an apoptosis inhibitor. BCL2 usually translocates to the immunoglobulin (IG) heavy chain (IGH) gene as t(14;18)(q32;q21.3) and rarely to IG light chain (IGK, IGL) loci as t(2;18)(p11;q21.3) or t(18;22)(q21.3;q11). The t(14;18) translocation is observed in 70-95% of follicular lymphoma cases and 20-30% of diffuse large B-cell lymphoma (DLBCL) cases. The MYC gene on chromosome band 8q24 acts as an accelerator of cell proliferation. MYC translocates to 14q32/IGH as t(8;14)(q24;q32) or less commonly to 2p11/IGK as t(2;8)(p11;q24) or 22q11/IGL as t(8;22)(q24;q11). The 8q24/MYC translocation is detected in nearly all Burkitt lymphoma (BL) and up to 10% of DLBCL cases. Both translocations rarely occur in an identical cell and this lymphoid malignancy is termed BCL2 and MYC dual-hit lymphoma/ leukemia (DHL). The pathological diagnosis in most cases of DHL with BCL2-IG and MYC-IG translocation is B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and BL, although DLBCL is most common in DHL with BCL2-IG and MYC-nonIG translocation. The frequency of DHL with BCL2 and MYC translocation is estimated at around 2% of all B-cell malignancies. The condition is characterized by elevated serum lactate dehydrogenase levels, the presence of B symptoms, bone marrow involvement, advanced disease stage, extranodal involvement, and central nervous system (CNS) involvement at presentation or disease progression. Despite treatment strategies including CNS-targeted therapy, the prognosis for DHL is extremely poor. In this review, the current knowledge of the clinicopathological status of DHL is summarized and discussed. 〔J Clin Exp Hematopathol 51 (1) : 7-12, 2011〕

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“…10 Infections may contribute to lymphomagenesis by promoting favorable conditions for lymphocyte transformation, such a increased proliferation or decreased apoptosis of lymphoid cells. 11 Direct lymphocyte transformation by a given microbial agent is the simplest scenario accounting for infection-associated lymphomas. Lymphotropic transforming viruses such as Epstein-Barr virus (EBV), human herpesvirus 8 (HHV8), and human Tlymphotropic virus 1 (HTLV-1) directly infect a subset of lymphoid cells in which they express viral oncogenes.…”

Section: Introductionmentioning

confidence: 99%

Infection-associated lymphomas derived from marginal zone B cells: a model of antigen-driven lymphoproliferation

Suarez

2006

Blood

398

296

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IntroductionThe geographic heterogeneity in the incidence of B-cell nonHodgkin lymphomas (NHLs) suggests that environmental factors such as infections might have a role in lymphomagenesis. 1,2 Because of the inherent genetic instability of lymphocytes, lymphoid proliferation increases the risk of transformation, and sustained activation of the lymphoid system, which can be observed during chronic infection, immunodeficiency, and autoimmunity, constitutes a risk factor for lymphomas. [3][4][5] Congenital and acquired immunodeficiencies associated with HIV infection and solid organ or hematopoietic transplantation increase the risk of developing B-cell NHLs. 6,7 Similarly, Sjögren syndrome and other autoimmune conditions are also associated with an increased risk of lymphomas. 8,9 Certain types of lymphomas are associated with specific microbial infections, and infection-associated lymphomas currently fall in diverse histopathologic categories (Table 1). 10 Infections may contribute to lymphomagenesis by promoting favorable conditions for lymphocyte transformation, such a increased proliferation or decreased apoptosis of lymphoid cells. 11 Direct lymphocyte transformation by a given microbial agent is the simplest scenario accounting for infection-associated lymphomas. Lymphotropic transforming viruses such as Epstein-Barr virus (EBV), human herpesvirus 8 (HHV8), and human Tlymphotropic virus 1 (HTLV-1) directly infect a subset of lymphoid cells in which they express viral oncogenes. [12][13][14] An alternative scenario to direct transformation of lymphocytes has more recently emerged for microbial species associated with lymphomas but that do not directly infect or transform lymphoid cells. They have in common the ability to persist chronically in host tissues and trigger a sustained lymphoid proliferation, giving a selective advantage to lymphoid clones that still remain dependent upon antigen stimulation. 15,16 According to this model, the microbial pathogen is neither intrinsically transforming nor oncogenic, but can be viewed as a chronic source of antigens increasing the proliferative rate of lymphoid effectors, hence fueling the transformation process. This model has emerged with the description of several lymphomas developing in the context of chronic antigen-dependent immune stimulation, among which H pylori-associated gastric mucosa-associated lymphoid tissue (MALT) lymphoma is the best characterized 15,17,18 (Figure 1). Precise elucidation of the mechanisms underlying this "indirect" lymphomagenesis as well as completion of the inventory of the microbial species driving these antigen-dependent lymphoproliferations may provide important clues for their early diagnosis and the rationalization of the therapeutic interventions for this subtype of lymphomas.This group of lymphomas often involves extranodal sitesnormally devoid of organized lymphoid tissue-and manifests initially as indolent low-grade proliferations, reminiscent of the normal lymphoid hyperplasia driven by a physiologic antigenic stimulation....

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Genetic and epigenetic factors involved in B‐cell lymphomagenesis

Cited by 27 publications

References 36 publications

Low-grade follicular lymphoma with t(14;18) presents a homogeneous disease entity otherwise the rest comprises minor groups of heterogeneous disease entities with Bcl2 amplification, Bcl6 translocation or other gene aberrances

Low-grade follicular lymphoma with t(14;18) presents a homogeneous disease entity otherwise the rest comprises minor groups of heterogeneous disease entities with Bcl2 amplification, Bcl6 translocation or other gene aberrances

BCL2 and MYC Dual-Hit Lymphoma/Leukemia

Infection-associated lymphomas derived from marginal zone B cells: a model of antigen-driven lymphoproliferation

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