Loss of the B-lineage–specific gene expression program in Hodgkin and Reed-Sternberg cells of Hodgkin lymphoma

Schwering, Ines; Bräuninger, Andreas; Klein, Ulf; Jungnickel, Berit; Tinguely, Marianne; Diehl, Volker; Hansmann, Martin‐Leo; Dalla‐Favera, Riccardo; Rajewsky, Klaus; Küppers, Ralf

doi:10.1182/blood-2002-03-0839

Cited by 348 publications

(298 citation statements)

References 50 publications

Supporting

Mentioning

278

Contrasting

Unclassified

Order By: Relevance

“…4,7,8,[28][29][30] In order to assess what previous studies have suggested about the lack of expression of transcription factors in classical Hodgkin's lymphoma, we performed an immunohistochemical analysis of OCT.1, OCT.2 and BOB.1 in 325 cases, using the tissue microarray technique and correlating the results to the histological subtype, B-cell marker expression, and Epstein-Barr virus presence. We decided to study the transcription factors on the neoplastic cells at Transcription factors in Hodgkin's lymphoma M García-Cosío et al the protein level because it might be more representative of their function than at the molecular level 28,31 and because there are few immunohistochemical studies including a large series of cases.…”

Section: Discussionmentioning

confidence: 99%

“…29,34 It is expressed in all B-cell stages of development from the pro-B-cell stage to the stage previous to plasma cell, where it is downregulated. 35 Previous studies [35][36][37] found a frequent BSAP expression in the HRS cells of classical Hodgkin's lymphoma.…”

Section: Discussionmentioning

confidence: 99%

“…Considering that PAX.5 regulates CD20, CD79a and OCT.2 expression, the low positivity rate of these markers found in our study is surprising. In order to explain a functional defect in BSAP protein of HRS cells, some studies have been attempted in search for mutations in PAX.5 gene, 29 but the absence of such mutations points to a defect of other essential factors in the control of B lineage of classical Hodgkin's lymphoma. Most of our cases expressed MUM.1, a transcription factor that belongs to the interferon regulatory factor family (IRF).…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Analysis of transcription factor OCT.1, OCT.2 and BOB.1 expression using tissue arrays in classical Hodgkin's lymphoma

et al. 2004

View full text Add to dashboard Cite

Hodgkin's lymphoma can be considered in most cases a B-cell lymphoma due to the presence of potentially functional immunoglobulin (Ig) gene rearrangements in the neoplastic cells. In contrast to lymphocytepredominant Hodgkin's lymphoma, Hodgkin/Reed-Sternberg (HRS) cells from classical Hodgkin's lymphoma have low frequency of B-cell marker expression and lack Ig light and Ig heavy messenger RNA. Recent studies have shown transcription machinery deficiency in Hodgkin's lymphoma caused by an absence of the transcription factors OCT.1, OCT.2 and/or BOB.1. By using the tissue microarray technique, we have performed an immunohistochemical study of OCT.1, OCT.2 and BOB.1 in 325 classical Hodgkin's lymphoma cases. The results have been correlated with the expression of the B-cell markers CD20, CD79a, B-cell-specific activator protein (BSAP) and MUM.1, the presence of Epstein-Barr virus and the histological subtype. The percentage of CD20 and CD79a positivity was low (18 and 18%, respectively), whereas MUM.1 and BSAP were positive in the majority of cases. Considering the positive cases with independence of the intensity of staining, 62% of them expressed OCT.2, 59% OCT.1 and 37% BOB.1. Nevertheless, when we considered only the strongly positive cases, the results were similar to those previously described by others. No statistical association was found between the transcription factor expression, histological subtype and Epstein-Barr virus presence. To our knowledge, this is the largest series of classical Hodgkin's lymphoma cases in which the expression of transcription factors has been studied. We have found a notorious percentage of cases displaying weak positivity for OCT.2 and BOB.1 factors in HRS cells. We propose that other mechanisms different from the absence of transcription factors OCT.2 and BOB.1 might be involved in the control of Ig transcription and B lineage in classical Hodgkin's lymphoma.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Analysis of transcription factor OCT.1, OCT.2 and BOB.1 expression using tissue arrays in classical Hodgkin's lymphoma

et al. 2004

View full text Add to dashboard Cite

show abstract

“…7,25,26 Several researchers have described a drastic loss of the B-cell-specific gene expression program in Hodgkin/Reed-Sternberg cells that may be related to downregulation of PAX5 mRNA. 27,28 This downregulation of gene expression most likely corresponds at the phenotypic level to decreased PAX5 protein expression and to less intense staining in tissue biopsies. The downregulation may also correspond to increased expression of non-B-lineage markers often detected in CHL that may confound its diagnosis.…”

Section: Pax5 In Undifferentiated Neoplasmsmentioning

confidence: 99%

The utility of PAX5 immunohistochemistry in the diagnosis of undifferentiated malignant neoplasms

et al. 2007

View full text Add to dashboard Cite

PAX5 is a B-cell transcription factor whose expression at the protein level is reliably detected by immunohistochemistry in routine biopsies. The purpose of this study was to investigate whether PAX5 immunohistochemistry has diagnostic benefit as a B-cell marker in the work-up of undifferentiated malignant neoplasms. Twenty-five cases previously diagnosed as undifferentiated malignant neoplasms were selected. In addition, 59 hematolymphoid and 884 non-hematolymphoid malignancies were studied such that the specificity of PAX5 immunohistochemistry could be addressed. Two of the 25 (8%) undifferentiated neoplasms showed diffuse staining for PAX5, which indicated a B-cell derivation for these neoplasms that was not appreciated at the time of initial diagnosis. PAX5 staining was detected in the vast majority of hematolymphoid tumors of Bcell derivation but only in 5 of 884 (less than 1%) non-hematolymphoid tumors. Our results further show that PAX5 may be the only detectable marker of B lineage in lymphomas that lack or show equivocal CD45RB and CD20 expression. We conclude that the addition of PAX5 to a panel of immunohistologic markers used in the interrogation of undifferentiated neoplasms is of diagnostic benefit. Its expression can also facilitate the diagnosis of classical and nodular lymphocyte-predominant Hodgkin lymphoma with atypical morphologic and immunohistologic features. Lastly, we have shown that the lack of its expression at the protein level in many epithelial and mesenchymal neoplasms renders PAX5 expression an extremely specific marker of the B lineage. Keywords: PAX5; B cell; non-Hodgkin lymphoma; Hodgkin lymphoma; undifferentiated neoplasm PAX5 (B-cell-specific activator protein, BSAP) is a member of the paired box domain gene family that encodes nuclear transcription factors important in development, differentiation, cell migration and proliferation. 1,2 PAX5 protein is expressed as a nuclear marker in B-lineage cells that span the differentiation spectrum from precursor B cells to early plasma cells. 3,4 The expression of PAX5 protein is also a useful lineage-specific marker in hematopoietic neoplasms arising from B cells. [5][6][7][8] Staining for PAX5 has additional utility in the diagnosis of B-cell malignancies that lack expression of commonly used pan-B-cell markers such as CD20 and CD79a. 9 In addition to its expression in B cells, PAX5 protein and/or mRNA has been reported to be expressed in normal and neoplastic cell types in the central nervous system, testis and bladder. 3,[10][11][12][13][14][15] B-cell malignancies may express PAX5 in the absence of expression of other pan-B-cell markers, suggesting that the inclusion of PAX5 in a panel of antibodies to assess undifferentiated malignant neoplasms may have diagnostic benefit. To address this possibility, we studied examples previously diagnosed as undifferentiated malignant neoplasms for PAX5 expression by immunohistologic methods. Hodgkin and non-Hodgkin lymphomas (NHLs) that lacked or showed equivocal staining for CD20 were also i...

show abstract

“…Lymphoma is a group of bewildering diseases in their limited effective therapy and untoward prognosis. Various approaches have been applied to clarify the pathogenesis of lymphoma, such as mRNA transcriptome,[1] miRNA targetome,[2] cell signaling,[3] gene translocation,[4] and Epstein-Barr virus infection,[5,6] etc. However, our understanding in development of neoplastic lymphoid cells is largely insufficient.…”

Section: Introductionmentioning

confidence: 99%

Perforin gene mutations in 77 Chinese patients with lymphomas

Ding

Yang

2013

World Journal of Emergency Medicine

View full text Add to dashboard Cite

BACKGROUND:Perforin gene (PRF1) mutations have been reported in patients with lymphoma, but the prevalence and characteristics of PRF1 mutation have not been identified in Chinese patients with lymphoma.METHODS:Seventy-seven patients with lymphoma, including 6 patients with Hodgkin lymphoma and 71 patients with non-Hodgkin lymphoma, were recruited. DNA samples from peripheral blood were used for PRF1 mutation detection by the PCR-sequencing method.RESULTS:Eleven novel PRF1 mutations were found in 8 of the 77 patients with lymphoma. Biallelic or compound monoallelic missense mutations in 3 patients indicated the severe impairment of perforin function, monoallelic missense mutations in 3 patients possibly contributed a genetic predisposition to malignancies, and synonymous mutations in 2 patients showed unknown significance.CONCLUSIONS:The frequency of EBV infection was similar in lymphoma patients with PRF1 mutations and those without the mutations. The same PRF1 mutations were also found in DNA samples from nails or hair follicles from 4 patients with PRF1 mutations, suggesting that these mutations may be of germ-line origin.

show abstract

Loss of the B-lineage–specific gene expression program in Hodgkin and Reed-Sternberg cells of Hodgkin lymphoma

Cited by 348 publications

References 50 publications

Analysis of transcription factor OCT.1, OCT.2 and BOB.1 expression using tissue arrays in classical Hodgkin's lymphoma

Analysis of transcription factor OCT.1, OCT.2 and BOB.1 expression using tissue arrays in classical Hodgkin's lymphoma

The utility of PAX5 immunohistochemistry in the diagnosis of undifferentiated malignant neoplasms

Perforin gene mutations in 77 Chinese patients with lymphomas

Contact Info

Product

Resources

About