Nodal marginal zone lymphoma: gene expression and miRNA profiling identify diagnostic markers and potential therapeutic targets

Arribas, Alberto J.; Campos-Martín, Yolanda; Gómez-Abad, Cristina; Algara, Patricia; Sánchez‐Beato, Margarita; Rodríguez-Pinilla, María; Montes‐Moreno, Santiago; Martínez, Nerea; Alves-Ferreira, J.; Piris, Miguel Á.; Mollejo, Manuela

doi:10.1182/blood-2011-02-339556

Cited by 89 publications

(72 citation statements)

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“…These findings confirm the similarity of splenic marginal zone lymphoma with the marginal zone. 12,[24][25][26] As already described in other low-grade lymphomas, 16 the inflammatory cytokines present in the microenvironment may be involved in the onset and progression of disease contributing to the survival of tumor cells, consistently with what is already known about the role of the inflammatory microenvironment in this lymphoma type.…”

Section: Discussionmentioning

confidence: 69%

“…Similarly, among the miRNAs with increased expression in nodal marginal zone lymphoma were several already known to be overexpressed in this lymphoma type, such as miR199a 16 (Table 2; Supplementary Table 5). …”

Section: Comparison Between Splenic and Nodal Marginal Zone Lymphomasmentioning

confidence: 95%

“…To compare the miRNA expression profile between splenic and nodal marginal zone lymphoma, we included 15 lymph nodes infiltrated by nodal marginal zone lymphoma that were included in a previous study by our group. 16 The main criterion for inclusion was the availability of frozen tissue from the diagnostic specimen in each case. Morphological examination and CD20 immunostaining revealed the cases in which at least 75% of the cells were tumoral in this study.…”

Section: Patients and Tissue Samplesmentioning

confidence: 99%

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Splenic marginal zone lymphoma: comprehensive analysis of gene expression and miRNA profiling

et al. 2013

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Splenic marginal zone lymphoma is a small B-cell neoplasm whose molecular pathogenesis is still essentially unknown and whose differentiation from other small B-cell lymphomas is hampered by the lack of specific markers. We have analyzed the gene expression and miRNA profiles of 31 splenic marginal zone lymphoma cases. For comparison, 7 spleens with reactive lymphoid hyperplasia, 10 spleens infiltrated by chronic lymphocytic leukemia, 12 spleens with follicular lymphoma, 6 spleens infiltrated by mantle cell lymphoma and 15 lymph nodes infiltrated by nodal marginal zone lymphoma were included. The results were validated by qRT-PCR in an independent series including 77 paraffin-embedded splenic marginal zone lymphomas. The splenic marginal zone lymphoma miRNA signature had deregulated expression of 51 miRNAs. The most highly overexpressed miRNAs were miR-155, miR-21, miR-34a, miR-193b and miR-100, while the most repressed miRNAs were miR-377, miR-27b, miR-145, miR-376a and miR-424. MiRNAs located in 14q32-31 were underexpressed in splenic marginal zone lymphoma compared with reactive lymphoid tissues and other B-cell lymphomas. Finally, the gene expression data were integrated with the miRNA profile to identify functional relationships between genes and deregulated miRNAs. Our study reveals miRNAs that are deregulated in splenic marginal zone lymphoma and identifies new candidate diagnostic molecules for splenic marginal zone lymphoma.

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Section: Discussionmentioning

confidence: 69%

Section: Comparison Between Splenic and Nodal Marginal Zone Lymphomasmentioning

confidence: 95%

Section: Patients and Tissue Samplesmentioning

confidence: 99%

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Splenic marginal zone lymphoma: comprehensive analysis of gene expression and miRNA profiling

et al. 2013

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“…73 Another study of 15 NMZLs and 16 FLs reported a rather homogeneous gene expression profile in NMZLs resembling marginal zone and memory B cells. 90 Compared to FL, NMZL showed overexpression of NF-κB-related and -binding genes (TRAF4, CD82), IL-32, histones, members of the TNF family (TACI, TNFRSF14), and genes involved in lymphocyte activation (TGFB1). FLs showed higher expression of germinal center markers (CD10, BCL6, GCET1, LMO2) in comparison to NMZL.…”

Section: Molecular Featuresmentioning

confidence: 99%

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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“…51,52 The expression program of marginal zone lymphomas shows that nodal and extranodal types share common profiles with upregulation of genes related to cell-cell and cell-extracellular matrix interactions. 53,54 Peripheral T-cell lymphomas. GEP studies in T-cell lymphomas have been able to recognize specific global expression patterns for the most common entities although they are more difficult to interpret, due to the lower frequency of these tumors and the heterogeneity of the tumor cell microenvironment.…”

Section: Characterization Of Known Entities and Recognition Of New Camentioning

confidence: 99%

Whole genome profiling and other high throughput technologies in lymphoid neoplasms—current contributions and future hopes

Campo

2013

Modern Pathology

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The development of high throughput technologies based on the knowledge of the human genome has opened the possibility to search for global genomic alterations in tumors responsible for their development and progression that may have important clinical implications. One of the major applications of this genomic knowledge has been the design of different types of microarray platforms for the analysis of DNA alterations and gene expression profiling (GEP). The main contributions of the DNA studies in lymphoid neoplasms include the definition of relatively characteristic genomic profiles for specific disease entities, the demonstration of common chromosomal alterations across entities, the identification of genes and pathways targeted by the altered chromosomal regions, and the identification of chromosomal alterations with prognostic implications. RNA GEP studies in these tumors have enhanced the molecular characterization of known entities and facilitated the recognition of new subtypes and categories of lymphoid neoplasms, the identification of new biomarkers and prognostic models, and the detection of oncogenic pathways with potential implications for targeted therapies. The recent development of the next generation sequencing (NGS) technologies and its application in lymphoid neoplasms already have provided an initial view of the complex landscape of somatic mutations in these tumors and some findings with important functional and clinical implications. This review addresses the major contributions and limitations of the microarray technologies in the understanding of lymphoid neoplasms and discusses how this knowledge may be transferred into the clinics. The initial results of the NGS studies are also presented.

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Nodal marginal zone lymphoma: gene expression and miRNA profiling identify diagnostic markers and potential therapeutic targets

Cited by 89 publications

References 38 publications

Splenic marginal zone lymphoma: comprehensive analysis of gene expression and miRNA profiling

Splenic marginal zone lymphoma: comprehensive analysis of gene expression and miRNA profiling

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

Whole genome profiling and other high throughput technologies in lymphoid neoplasms—current contributions and future hopes

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