t(X;14)(p11.4;q32.33) is recurrent in marginal zone lymphoma and up-regulates GPR34

Baens, Mathijs; Ferreiro, Julio Finalet; Tousseyn, Thomas; Urbánková, Helena; Michaux, Lucienne; Leval, Laurence de; Dierickx, Daan; Wolter, Pascal; Vandenberghe, Peter; Wolf-Peeters, Christiane De; Włodarska, Iwona

doi:10.3324/haematol.2011.052639

Cited by 39 publications

(24 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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. …”

mentioning

confidence: 88%

See 1 more Smart Citation

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

Brand

Krieken

2013

Haematologica

View full text Add to dashboard Cite

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...

show abstract

mentioning

confidence: 88%

“…Figure 3 summarizes gains and losses of chromosome regions and whole chromosomes reported in the literature. 12,15,36,[76][77][78][79][80][81][82][83][84][85][86] Gains of chromosome 1q, 2p, 3p, 3q, 6p, and 6q are most frequent, as are losses of 1q and 6q. Chromosomes 3, 12, and 18 most often show trisomy.…”

mentioning

confidence: 99%

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

Brand

Krieken

2013

Haematologica

View full text Add to dashboard Cite

show abstract

“…While this manuscript was in review, Baens et al published the identification of 4 additional cases of lymphoma, 2 MALT, 1 NMZBCL, and 1 gastric DLBCL, that carry (X;14)(p11.4;q32.33) further highlighting the potential significance of this translocation in NHL. 8 When Baens et al analyzed the impact of GPR34 overexpression they did not detect ERK activation. 8 However, in their model, overexpression of GPR34 was only measured by PCR and it is not yet clear whether the GPR34 protein was detected on the cell surface.…”

Section: Discussionmentioning

confidence: 97%

“…MALT lymphoma is genetically unique and 5 mutually exclusive chromosomal translocations have been identified in this disease thus far: t(11;18)/ BIRC3(aka API2)-MALT1, 2-4 t(1;14)/IGH-BCL10, 5 t(14;18)/IGH-MALT1 6 t(3;14)/IGH-FOXP1, 7 and t(X;14)/IGH-GPR34. 8 Despite this genetic heterogeneity, all but one of the translocations affect the NF-B signaling pathway. 9 However, the known translocations are only present in a subset of cases suggesting that additional uncharacterized translocations or other genetic events may exist that contribute to disease development.…”

Section: Introductionmentioning

confidence: 99%

t(X;14)(p11;q32) in MALT lymphoma involving GPR34 reveals a role for GPR34 in tumor cell growth

Ansell

Akasaka

McPhail³

et al. 2012

Blood

View full text Add to dashboard Cite

Genetic aberrations, including trisomies 3 and 18, and well-defined IGH translocations, have been described in marginal zone lymphomas (MZLs); however, these known genetic events are present in only a subset of cases. Here, we report the cloning of an IGH translocation partner on chromosome X, t(X;14)(p11.4;q32) that deregulates expression of an poorly characterized orphan G-protein-coupled receptor, GPR34. Elevated GPR34 gene expression was detected independent of the translocation in multiple subtypes of non-Hodgkin lymphoma and distinguished a unique molecular subtype of MZL. Increased expression of GPR34 was also detected in tissue from brain tumors and surface expression of GPR34 was detected on human MZL tumor cells and normal immune cells. Overexpression of GPR34 in lymphoma and HeLa cells resulted in phosphorylation of ERK, PKC, and CREB; induced CRE, AP1, and NF-κB-mediated gene transcription; and increased cell proliferation. In summary, these results are the first to identify a role for a GPR34 in lymphoma cell growth, provide insight into GPR34-mediated signaling, identify a genetically unique subset of MZLs that express high levels of GPR34, and suggest that MEK inhibitors may be useful for treatment of GPR34-expressing tumors.

show abstract

“…GPR34 belongs to the P2Y 12 -like receptor group, and its expression levels have been related to impaired immunity (6,11) and development of lymphoma and gastric cancer (35)(36)(37)(38). Upregulation of the receptor has also been linked to neuroinflammation (9).…”

Section: Discussionmentioning

confidence: 99%

Dendritic Cells Regulate GPR34 through Mitogenic Signals and Undergo Apoptosis in Its Absence

Jäger

Schulz

Lede

et al. 2016

The Journal of Immunology

View full text Add to dashboard Cite

Dendritic cells (DCs) are specifically equipped with the G protein–coupled receptor 34 (GPR34). Tight regulation of GPR34 gene expression seems highly important for proper immunological functions, because the absence of this receptor leads to an alteration of the immune response, whereas overexpression was reported to be involved in neuroinflammation. However, the regulatory mechanism of GPR34 expression has not yet been investigated. Whole-transcriptome RNA sequencing analysis from spleens and DCs of GPR34 knockout and wild-type mice, combined with protein–protein interaction data, revealed functional modules affected by the absence of this receptor. Among these, NF-κB, MAPK, and apoptosis-signaling pathways showed high significance. Using murine DCs we experimentally show that NF-κB and MAPK pathways are involved in the downregulation of GPR34. DCs lacking GPR34 have a higher caspase-3/7 activity and increased apoptosis levels. Our study reveals a novel role of GPR34 in the fate of DCs and identifies a regulatory mechanism that could be relevant for treatment of GPR34-overexpressing pathologies, such as neuroinflammatory or cancer conditions.

show abstract

t(X;14)(p11.4;q32.33) is recurrent in marginal zone lymphoma and up-regulates GPR34

Abstract: embedded tissue sections. As positive controls, normal testis and bone marrow biopsies from patients with mastocytosis were used. Sections were stained according to the manufacturer's recommendations, and IHC results were visualized using the En Vision system (Dako Denmark A/S).

Cited by 39 publications

References 15 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

t(X;14)(p11;q32) in MALT lymphoma involving GPR34 reveals a role for GPR34 in tumor cell growth

Dendritic Cells Regulate GPR34 through Mitogenic Signals and Undergo Apoptosis in Its Absence

Contact Info

Product

Resources

About