Association of Ig/BCL6 translocations with germinal center B lymphocytes in human lymphoid tissues: implications for malignant transformation

Yang, Xuwei; Lee, Koutetsu; Said, Jonathan; Gong, Xun; Zhang, Ke

doi:10.1182/blood-2006-03-011536

Cited by 39 publications

(6 citation statements)

References 30 publications

(46 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Non-physiological BCL6 expression is achieved through various mechanisms, including translocations to facilitate BCL6 expression from different germinal centerexpressed genes, including various Ig genes (103-106). Intriguingly, and reminiscent of BCL2 translocations (107), Ig-BCL6 translocations can be detected in germinal center-derived B-cells from apparently healthy individuals, suggesting that BCL6 overexpression is not a potent driver of lymphomagenesis, per se (4,15,16,108). In keeping with these observations, transgenic BCL6 expression off the Il promoter in mice leads to increased germinal center formation, perturbed postgerminal center differentiation and the development of a lympho-proliferative disease, which funnels into the development of a DLBCL-like disease in these animals (109).…”

Section: Additional Alterations Lead To a Block In Plasma Cell Differmentioning

confidence: 99%

Rewired NFκB signaling as a potentially actionable feature of activated B‐cell‐like diffuse large B‐cell lymphoma

Knittel

Liedgens

Korovkina

et al. 2016

European J of Haematology

View full text Add to dashboard Cite

Diffuse large B-cell lymphoma (DLBCL) is the most common type of aggressive lymphoma in the Western world and remains a clinical challenge. Two types of DLBCL are distinguishable, namely a germinal center B-cell-like phenotype (GCB) and an activated B-cell-like phenotype (ABC). Particularly ABC-DLBCL is difficult to treat, as this subentity typically displays resistance against frontline chemo-immune therapy. Through the availability of novel experimental technologies, such as next-generation sequencing and cutting-edge mouse models, we recently caught an unprecedentedly detailed glimpse at the genomic and biological features of ABC-DLBCL. Currently, a picture is emerging which suggests that ABC-DLBCL critically depends on sustained activity of the NFjB pathway, which, among others, is achieved through numerous distinct genetic aberrations, including CD79A/B-, CARD11-, and MYD88 mutations. Further genomic aberrations include amplifications of BCL2 and inactivating mutations in PRMD1. These molecular insights have spurred the development of novel autochthonous mouse models that faithfully mimic the biology and genetics of human ABC-DLBCL and could serve as preclinical platforms in future experiments. Furthermore, our genomic understanding of the disease now enables us to develop and validate novel targeted therapeutic intervention strategies that aim at decapitating non-physiological NFjB activity and repressing anti-apoptotic BCL2 signaling. In this review, we highlight these recent developments and make suggestions for further tool development and the design and stratification of future clinical trials.

show abstract

Section: Additional Alterations Lead To a Block In Plasma Cell Differmentioning

confidence: 99%

Rewired NFκB signaling as a potentially actionable feature of activated B‐cell‐like diffuse large B‐cell lymphoma

Knittel

Liedgens

Korovkina

et al. 2016

European J of Haematology

View full text Add to dashboard Cite

show abstract

“…5,6 However, aberrant expression of BCL2 is not sufficient in mice for full lymphoma transformation and t(14;18) or t (3;14) are observed in non-tumoral B cells, indicating that accumulation of other genetic alterations is required for the malignant transformation. 7,8 Array-based comparative genomic hybridization (array CGH) has the potential to detect these additional aberrations that play an important role in the development and progression of lymphomas. Using this approach, it was shown that recurrent genomic imbalances are related to the cell of origin or correlated with the prognosis.…”

Section: Introductionmentioning

confidence: 99%

Detection of somatic quantitative genetic alterations by multiplex polymerase chain reaction for the prediction of outcome in diffuse large B-cell lymphomas

Jardin¹,

Ruminy²,

Kerckaert³

et al. 2008

Haematologica

View full text Add to dashboard Cite

BackgroundGenomic gains and losses play a crucial role in the development of diffuse large B-cell lymphomas. High resolution array comparative genomic hybridization provides a comprehensive view of these genomic imbalances but is not routinely applicable. We developed a polymerase chain reaction assay to provide information regarding gains or losses of relevant genes and prognosis in diffuse large B-cell lymphomas.

show abstract

“…FFH is observed in many models and lymphomas occurring later harbour additional genetic alterations [42,[45][46][47]. Yang et al [13] recently also described IGH/BCL6 rearrangements in GC Bcells of healthy humans by PCR-based assays. Our findings of frequent 14q32 and 3q27 aberrations, localized to the GC in a few cases analysed, are supportive of the aforementioned etiopathogenic concepts.…”

Section: Discussionmentioning

confidence: 92%

“…However, by using sensitive methods, 'NHL associated translocations', especially IGH/BCL2 [11,12], IGH/BCL6 [13], NPM/ ALK and ATIC/ALK [14] can be detected in LN or peripheral blood of healthy individuals. Although, the developmental stage or time of acquisition of t(14;18) is still debated, the currently favoured view is that it results from abnormalities of VDJ recombination in bone marrow B-cell precursors [12].…”

Section: Introductionmentioning

confidence: 99%

Cytogenetic abnormalities in reactive lymphoid hyperplasia: byproducts of the germinal centre reaction or indicators of lymphoma?

Sevilla

Murty

Sun

et al. 2011

Hematological Oncology

View full text Add to dashboard Cite

Non-random karyotypic abnormalities associated with non-Hodgkin lymphomas (NHLs) have been described in cases of reactive lymphoid hyperplasia (RLH). However, the frequency and types of cytogenetic aberrations detected and their clinical relevance are unknown. To address these questions, we undertook a retrospective analysis of a large series of RLH diagnosed at our institute over 8 years. Cytogenetic abnormalities were identified in 20 of 116 (17%) cases with informative karyotypes, comprising 14 (70%) structural and 11 (55%) numerical changes. Clonal (n = 14, 70%) and non-clonal (n = 6, 30%) abnormalities were observed. Aberrations of chromosome 14 were the most frequent (n = 8, 42%, 7 represented IgH translocations), followed by chromosome 3 (n = 4, 3 represented BCL6 translocations), and chromosome 12 (n = 4). Abnormal karyotypes were most often associated with florid follicular hyperplasia. Isolated lymphoid organ (lymph node, tonsil or spleen) enlargement (12/20, 60%) was more common, no specific etiology was identified in 10/20 (50%) cases and only 1 of 18 patients with clinical follow-up (range 2-107 months, median 60 months) developed lymphoma. In our experience, cytogenetic abnormalities involving loci associated with B-cell NHL are not infrequently detected in RLH. Their occurrence portends low risk for lymphomagenesis, however longer follow-up is prudent to further evaluate the natural history of such cases.

show abstract

Association of Ig/BCL6 translocations with germinal center B lymphocytes in human lymphoid tissues: implications for malignant transformation

Cited by 39 publications

References 30 publications

Rewired NFκB signaling as a potentially actionable feature of activated B‐cell‐like diffuse large B‐cell lymphoma

Rewired NFκB signaling as a potentially actionable feature of activated B‐cell‐like diffuse large B‐cell lymphoma

Detection of somatic quantitative genetic alterations by multiplex polymerase chain reaction for the prediction of outcome in diffuse large B-cell lymphomas

Cytogenetic abnormalities in reactive lymphoid hyperplasia: byproducts of the germinal centre reaction or indicators of lymphoma?

Contact Info

Product

Resources

About