<i>BCL6</i> gene rearrangements also occur in marginal zone B‐cell lymphoma

Dierlamm, Judith; Pittaluga, Stefania; Stul, Michel; Włodarska, Iwona; Michaux, Lucienne; Thomas, José; Verhoef, Gregor; Verhest, Alain; Depardieu, C; Jj, Cassiman; Hagemeijer, Anne; Wolf‐Peeters, Chris De; Berghe, Herman Van den

doi:10.1046/j.1365-2141.1997.2703087.x

Cited by 48 publications

(26 citation statements)

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“…The translocations that have been described in NMZL do not include regions harboring these genes. 12,15,76,77,79,82,[85][86][87][88][89] Although Dierlamm and colleagues did not detect translocations involving BCL6 in NMZL, 12,20,77 the karyotypes of 3 of 21 patients described by TraverseGlehen et al do suggest translocations involving BCL6. …”

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Recognizing nodal marginal zone lymphoma: recent advances and pitfalls. A systematic review

Brand

Krieken

2013

Haematologica

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The diagnosis of nodal marginal zone lymphoma is one of the remaining problem areas in hematopathology. Because no established positive markers exist for this lymphoma, it is frequently a diagnosis of exclusion, making distinction from other low-grade B-cell lymphomas difficult or even impossible. This systematic review summarizes and discusses the current knowledge on nodal marginal zone lymphoma, including clinical features, epidemiology and etiology, histology, and cytogenetic and molecular features. In particular, recent advances in diagnostics and pathogenesis are discussed. New immunohistochemical markers have become available that could be used as positive markers for nodal marginal zone lymphoma. These markers could be used to ensure more homogeneous study groups in future research. Also, recent gene expression studies and studies describing specific gene mutations have provided clues to the pathogenesis of nodal marginal zone lymphoma, suggesting deregulation of the nuclear factor kappa B pathway. Nevertheless, nodal marginal zone lymphoma remains an enigmatic entity, requiring further study to define its pathogenesis to allow an accurate diagnosis and tailored treatment. However, recent data indicate that it is not related to splenic or extranodal lymphoma, and that it is also not related to lymphoplasmacytic lymphoma. Thus, even though the diagnosis is not always easy, it is clearly a separate entity. ABSTRACT© F e r r a t a S t o r t i F o u n d a t i o n . Epidemiology and etiology NMZL is a rare lymphoma, accounting for 1.5-1.8% of lymphoid neoplasms. 9,10 The incidence of NMZL appears to be increasing, which is most likely due to a 'real' increase, rather than better recognition.11 Most studies report a median age around 60 years with a wide age distribution ranging from adolescence to patients over 90 years old. [9][10][11][12][13][14][15][16][17][18][19][20] Both sexes are affected with approximately equal frequency.Morphologically, NMZL resembles EMZL. EMZL is well known for its association with conditions that provide a chronic stimulation to the immune system, including chronic infections (e.g. Helicobacter pylori infection in gastric EMZL) and autoimmune conditions (e.g. salivary gland EMZL in Sjögren's syndrome). From this, one could hypothesize that NMZL, or a subset of NMZLs, might also be caused by specific chronic inflammatory conditions. Indeed, infections and autoimmune disorders have been reported in association with NMZL, but this evidence remains far from sufficient to establish a definitive role for these stimuli in lymphomagenesis. Recently, we encountered a case of what we had referred to as NMZL lymphoma in an axillary lymph node. However, we detected H. pylori by PCR analysis and a gastric biopsy revealed EMZL. This case implies that without extensive workup, including gastric biopsies, one cannot be sure that a case of NMZL really represents this entity.Hepatitis C virus (HCV) has been reported in a subset of NMZL patients. In an early but small study, monocytoid B-cell lymph...

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confidence: 88%

“…[9][10][11][12][13][14][15][16][17][18][19][20] Both sexes are affected with approximately equal frequency.…”

Section: Introductionmentioning

confidence: 99%

Recognizing nodal marginal zone lymphoma: recent advances and pitfalls. A systematic review

Brand

Krieken

2013

Haematologica

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“…Part of these cases was included in previous studies. 5,7,9,[14][15][16][17] Gastric endoscopic biopsies were included in this study on condition that clonal Ig heavy chain rearrangement was demonstrated to support the diagnosis of a MALT lymphoma. All cases were reviewed and diagnosed as extranodal marginal zone lymphomas according to the recent criteria of the WHO.…”

Section: Case Selectionmentioning

confidence: 99%

MALT1 and BCL10 aberrations in MALT lymphomas and their effect on the expression of BCL10 in the tumour cells

et al. 2006

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Among the genetic abnormalities reported to occur in mucosa-associated lymphoid tissue (MALT) lymphomas, the three translocations t(11;18)(q21;q21), t(1;14)(p22;q32) and t(14;18)(q32;q21) are of particular interest because they appear to be specific for, or at least closely related to this type of B-cell non-Hodgkin's lymphoma. These translocations affect the MALT1 (18q21) and BCL10 (1p22) genes. We retrieved 77 consecutive biopsies of MALT lymphomas (documented with frozen material) over a 10-year period and investigated these cases for the presence of these three translocations with fluorescence in situ hybridisation, along with the immunohistochemical analysis of the intracellular localisation of the BCL10 protein. The above-listed translocations occurred mutually exclusive and were detected in 10, 1 and 3% of the cases, respectively (the latter incidence being much lower than in the previously reported studies by one single group). These genetic rearrangements corresponded well with the aberrant subcellular localisation of the BCL10 protein as found by immunohistochemistry: t(11;18)(q21;q21) and (1;14)(p22;q32) were marked by a, respectively, moderate to strong nuclear BCL10 staining pattern while t(14;18)(q32;q21)-positive MALT lymphomas were characterised by a perinuclear BCL10 staining pattern. This study further supports the close interaction between the MALT1 and BCL10 proteins in the pathogenesis of MALT lymphomas and may indicate that BCL10 immunohistochemistry is a simple technique to identify those MALT lymphoma cases with an underlying genetic aberration. 1 It is characterised by several recurrent chromosomal aberrations including t(1;14)(p22;q32), t(11;18) (q21;q21), t(14;18)(q32;q21), t(3;14)(p13;q32), and by trisomy 3 and 18.The t(1;14)(p22;q32) results in deregulation of the BCL10 gene after its juxtaposition with the regulatory sequences of the immunoglobulin heavy chain gene cluster (IGH).2 BCL10 encodes a 32 kDa apoptosis regulatory molecule, characterised by an amino-terminal caspase recruit domain (CARD) motif and a Ser/Thr-rich carboxyl terminus of unknown function.3 Monoclonal antibodies raised against the BCL10 protein demonstrate cytoplasmic expression of BCL10 in lymphoid tissue and in breast epithelium. 4 In normal lymphoid tissue, BCL10 is expressed exclusively in the cytoplasm of germinal centre and marginal zone B cells. In MALT lymphomas, the BCL10 expression might be observed in the nucleus as well. Nuclear BCL10 expression has been linked to the presence of t(1;14)(p22;q32) or t(11;18)(q21;q21), but the mechanisms of the aberrant nuclear localisation of BCL10 in malignant B cells remain unclear. 5,6The MALT1 gene is directly involved in the MALT lymphoma-associated chromosomal translocations t(11;18)(q21;q21) and t(14;18)(q32;q21). The first translocation is the most common structural chromosomal abnormality in gastric MALT lymphoma. 7,8 It leads to the generation of a fusion protein comprising the three BIR (baculovirus inhibitor of apoptosis protein repeat) domains present in...

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“…Several genes located at chromosome 3 have been proposed as possibly responsible for these alterations, including BCL6 and FOXP1. 31,40,[45][46][47][48] Given that the BCL6 gene is involved in diffuse large B-cell lymphomas, it is possible that this gene also contributes to the pathogenesis of other lymphomas with trisomy 3, but the actual target gene in MALT lymphoma with trisomy 3 has not yet been identified. Recently, p16 gene methylation was detected in 60% of MALT lymphoma cases, and it was also suggested that p16 methylation is not associated with tumor progression, but may be an early event in MALT lymphomagenesis.…”

Section: Molecular Genetics Of Mucosa-associated Lymphoid Tissue Lympmentioning

confidence: 99%

Molecular pathogenesis of MALT lymphoma: two signaling pathways underlying the antiapoptotic effect of API2-MALT1 fusion protein

2006

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At least three recurrent chromosomal translocations, t(11;18)(q21;q21), t(1;14)(p22;q32), t(14;18)(q32;q21), involving the API2-MALT1 fusion protein, BCL10 and MALT1, have been implicated in the pathogenesis of mucosa-associated lymphoid tissue (MALT) lymphoma. Several lines of evidence indicated that both BCL10 and MALT1 are required for nuclear factor kappa B (NF-jB) activation by antigen receptor stimulation in lymphocytes, and API2-MALT1 can bypass this BCL10/MALT1 signaling pathway. Nuclear factor kappa B activation may contribute to antiapoptotic effect through NF-jB-mediated upregulation of apoptotic inhibitor genes. We recently demonstrated that API2-MALT1 can induce transactivation of the API2 gene through NF-jB activation, thus highlighting a positive feedback-loop mechanism of self-activation by upregulating its own expression in t(11;18) MALT lymphomas. We also demonstrated that API2-MALT1 possesses an antiapoptotic effect, in part, through its direct interaction with apoptotic regulators. These findings therefore led us to hypothesize that the antiapoptotic effect by API2-MALT1 may be mediated by its interaction with apoptotic regulators, on the one hand, and by NF-jB-mediated upregulation of apoptotic inhibitor genes on the other. We also found that BCL10 and MALT1 are shuttling between nucleus and cytoplasm, and that MALT1 can regulate the subcellular location of BCL10. Leukemia (2006) 20, 929-936.

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BCL6 gene rearrangements also occur in marginal zone B‐cell lymphoma

Cited by 48 publications

References 34 publications

Recognizing nodal marginal zone lymphoma: recent advances and pitfalls. A systematic review

Recognizing nodal marginal zone lymphoma: recent advances and pitfalls. A systematic review

MALT1 and BCL10 aberrations in MALT lymphomas and their effect on the expression of BCL10 in the tumour cells

Molecular pathogenesis of MALT lymphoma: two signaling pathways underlying the antiapoptotic effect of API2-MALT1 fusion protein

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