The Correlation Between Non-Hodgkin Lymphoma and Expression Levels of B-Cell Activating Factor and Its Receptors

Abstract Abstract 4633 Background: Golgins are proteins of the Golgi complex. Several Golgins have been implicated in apoptosis. Expression of Golgin-84, a Golgin protein, is altered in apoptotic WEHI-231, a B-cell lymphoma line, suggesting that Golgin-84 may play a role in lymphoid tumorigenesis. Here, we aimed to determine the expression levels of Golgin-84 in human primary non-Hodgkin lymphomas and plasma cell myeloma. Design: Golgin-84 expression was investigated in non-Hodgkin lymphoma cell lines by using Western blot analysis and polyclonal antibodies. Using immunohistochemical stains, Western blotting analysis and Q-PCR, Golgin-84 expression was assessed in 5 reactive lymph nodes, 149 cases of primary non-Hodgkin lymphoma and 28 cases of primary plasma cell myeloma. Results: Immunohistochemical stains, Western blotting analysis and Q-PCR on 5 reactive lymph nodes demonstrated that Golgin-84 was expressed at low levels in lymphoid cells of germinal centers, mantle cells, marginal zones, and interfollicular areas. Golgin-84 was variably expressed in non-Hodgkin lymphoma cell lines tested, with the highest levels in cells from high-grade tumors (e.g. anaplastic large cell lymphoma; ALCL, Diffuse large B-cell lymphoma (DLBCL), ALCL and peripheral T-cell lymphoma unspecified (PTCL)) and the lowest levels in mantle cell lymphoma (MCL) cells. DLBCL, ALCL and PTCL frequently showed high expression of Golgin-84. Most lymphoplasmacytic lymphomas (LPL) and plasma cell myeloma (PCM) expressed high levels of Golgin-84. Expression levels of Golgin-84 were lower in MCL and low-grade B-cell non-Hodgkin lymphomas, including chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), follicular lymphoma (FL), and marginal zone lymphoma (MZL). Conclusions: Golgin-84 expression levels are low in lymphoid cells of normal lymph nodes. Most (>90%) cases of LPL and PCM, and at least half of cases of DLBCL, ALCL and PTCL express high levels of Golgin-84. These findings suggest that Golgin-84 may be involved in tumorigenesis or lymphoma progression, particularly in neoplasms with plasmacytic differentiation. Disclosures: No relevant conflicts of interest to declare.

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Genetic Variation in B-Cell–Activating Factor Is Associated with an Increased Risk of Developing B-Cell Non–Hodgkin Lymphoma

Cancer Research ◽

10.1158/0008-5472.can-08-4915 ◽

2009 ◽

Vol 69 (10) ◽

pp. 4217-4224 ◽

Cited By ~ 45

Author(s):

Anne J. Novak ◽

Susan L. Slager ◽

Zachary S. Fredericksen ◽

Alice H. Wang ◽

Michelle M. Manske ◽

...

Keyword(s):

Genetic Variation ◽

B Cell ◽

Hodgkin Lymphoma ◽

Non Hodgkin Lymphoma ◽

B Cell Activating Factor ◽

Increased Risk

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Expression levels of TWIST1 are associated with the clinicopathological stage of B-cell non-Hodgkin lymphoma

Experimental and Therapeutic Medicine ◽

10.3892/etm.2014.1962 ◽

2014 ◽

Vol 8 (5) ◽

pp. 1489-1493

Author(s):

CUNDONG JIA ◽

LIPING LIANG ◽

LILI YANG ◽

FENG ZHAO ◽

JINGPING BAI

Keyword(s):

B Cell ◽

Hodgkin Lymphoma ◽

Expression Levels ◽

Non Hodgkin Lymphoma

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Differences in the C13orf25 miRNA Cluster in Non-Hodgkin Lymphoma and Normal B-Cell Subtypes.

Blood ◽

10.1182/blood.v110.11.3586.3586 ◽

2007 ◽

Vol 110 (11) ◽

pp. 3586-3586

Author(s):

Jan-Lukas Robertus ◽

Miao Wang ◽

Geert Harms ◽

Tjasso Blokzijl ◽

Rikst Nynke Schakel ◽

...

Keyword(s):

B Cells ◽

B Cell ◽

Hodgkin Lymphoma ◽

Cell Lymphoma ◽

Expression Patterns ◽

Expression Level ◽

Expression Levels ◽

Qrt Pcr ◽

Non Hodgkin Lymphoma ◽

B Cell Subsets

Abstract Introduction Amplification of chromosome 13q31 is a frequent occurrence in lymphoma and solid tumors. The C13orf25 gene at 13q31.3 is the primary miRNA transcript for seven miRNAs. This specific cluster of miRNAs is sequentially related to the homologous miR-106a-92 cluster on chromosome X and the miR-106b-25 cluster on chromosome 7. The miR17-92 cluster has been shown to be over expressed in various non-Hodgkin Lymphoma (NHL). As a specific group of miRNAs which are derived from the same primary miRNA transcript, each miRNA in the cluster may be expected to show a similar expression level. However expression patterns vary markedly in different cancers. Aim of study To compare the expression pattern of the C13orf25 gene and the miRNAs in normal and malignant B-cells. Methods and Materials 51 cases of Ann Abour stage I and II primary diffuse large B-cell lymphoma (DLBCL) were collected together with 29 cases of B-CLL. All samples were examined for expression of miRNA miR-18a, -19, -20a, 17-3p, -17-5p and -92 and the C13orf 25 gene. Expression levels of the mature miRNAs were determined by qRT-PCR using Taqman miRNA assays. The level of C13orf25 was also determined by qRT-PCR using random primers and a Sybergreen probe. Results were compared by using 2−ΔCt and 2−ΔΔCt. Normal B-cell subpopulations were isolated from fresh tonsils obtained during routine pediatric tonsillectomies. B-cell subsets were stained accordingly and sorted by FACS. Results Comparison of the miRNA pattern (2−ΔCt) revealed that DLBCL have the highest expression level of miR-19b and that B-CLL shows a relative high expression level of miR-92. Normal naïve, germinal center and memory B-cells all show a similar expression pattern with miR-92 having the highest expression level. Remarkably a low expression level of miR-19b is seen in all three B-cell populations in contrast to DLBCL. Comparing the relative expression levels (2−ΔΔCt) of both NHL for each individual miRNA shows that B-CLL has a significantly higher level of expression for miR-19a. In DLBCL miR-17-5p, miR-18a and miR-20a have the highest expression levels. Currently 20 Mantle cell lymphoma are also being analyzed for the C13orf25 miRNAs cluster. Conclusion Our results show that both of the NHL B-cell malignancies and the B-cell subsets have different expression patterns of the individual levels of the 7 miRNAs contained in the same C13orf25 cluster. The relative expression levels of certain miRNAs from the same primary transcript are different in various NHL. Although there are no marked differences in the normal B-cell subsets for the C13orf25 cluster, further profiling revealed various different expression levels of other miRNAs. These findings may point towards a difference in processing efficiency or stability of miRNAs in the C13orf25 cluster leading to differences in pathogenesis specific for each malignancy even in cells of similar origin and differentiation stage.

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