Somatic mutation analysis of IgH variable regions reveals that tumor cells of most parafollicular (monocytoid) B-cell lymphoma, splenic marginal zone B-cell lymphoma, and some hairy cell leukemia are composed of memory B lymphocytes

Miranda, Roberto N.; Cousar, John B.; Hammer, Richard; Collins, Robert D.

doi:10.1016/s0046-8177(99)90010-2

Cited by 60 publications

(40 citation statements)

References 32 publications

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“…[40][41][42][43] This difference could be derived from the different criteria used to select cases, the difficulty of accurately recognizing cases of SMZL, or it may also be dependent on the choice of the bcl-6 gene in this series, instead of IgV H . To avoid bias deriving from a low representation of tumoral cells in the analyzed samples, we only studied DNA extracted from splenic samples in which the percentage of B cells was shown to represent over 70% of the cells included in the sample.…”

Section: Discussionmentioning

confidence: 99%

Molecular heterogeneity of splenic marginal zone lymphomas: analysis of mutations in the 5′ non-coding region of the bcl-6 gene

Mollejo

Villuendas

et al. 2001

Leukemia

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Splenic marginal zone lymphoma (SMZL) has been recognized as a distinctive type of small B cell lymphoma, and defined on the basis of its morphological, phenotypic, clinical and molecular characteristics. In spite of this, the borders of the entity, the homogeneity of the cases and the presumably cell origin of SMZL remain controversial issues. The frequency of mutation in the 5′ non-coding region of the bcl-6 gene has been used as a marker of germinal center derivation, which may be used to establish the molecular heterogeneity of different non-Hodgkin lymphoma (

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Section: Discussionmentioning

confidence: 99%

Molecular heterogeneity of splenic marginal zone lymphomas: analysis of mutations in the 5′ non-coding region of the bcl-6 gene

Mollejo

Villuendas

et al. 2001

Leukemia

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“…In NMZL, multiple studies have shown biased use of immunoglobulin heavy chain VH families VH3 and VH4, in particular VH4-34. 13,15,[28][29][30][31] Preferential use of VH3-34 is associated with Epstein-Barr virus and cytomegalovirus in patients with chronic lymphocytic leukemia. 32 In NMZL, an association with these viruses has not been established.…”

Section: Epidemiology and Etiologymentioning

confidence: 99%

“…However, the precise B-cell of origin of NMZL remains poorly defined and it has been suggested that NMZL can arise from different subsets of mature B cells, not necessarily being marginal zone B cells. Multiple small studies have examined the presence of somatic hypermutation (SHM), which was detected in the large majority of cases (in approximately 85%), 13,15,[28][29][30][31]42 suggesting a (post-)germinal center B cell. However, less than half the cases showed evidence of antigen selection.…”

Section: Cell Of Originmentioning

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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“…Although earlier reports demonstrated that cells from all SMZL cases had somatic mutations of the IgVH, suggesting that these tumors arise from memory postgerminal center B cells, subsequent studies have revealed a significant molecular heterogeneity [14-16, [25][26][27][28]. In SMZL, as in other B-cell neoplasms, the IgVH mutational status does not play a diagnostic role but has provided insights in the pathogenesis of the disease.…”

Section: Editorialmentioning

confidence: 99%

Clinical and biological diversity of splenic marginal zone lymphoma

Matutes

2009

Expert Review of Anticancer Therapy

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Somatic mutation analysis of IgH variable regions reveals that tumor cells of most parafollicular (monocytoid) B-cell lymphoma, splenic marginal zone B-cell lymphoma, and some hairy cell leukemia are composed of memory B lymphocytes

Cited by 60 publications

References 32 publications

Molecular heterogeneity of splenic marginal zone lymphomas: analysis of mutations in the 5′ non-coding region of the bcl-6 gene

Molecular heterogeneity of splenic marginal zone lymphomas: analysis of mutations in the 5′ non-coding region of the bcl-6 gene

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

Clinical and biological diversity of splenic marginal zone lymphoma

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