Immunoglobulin gene rearrangements and expression in diffuse histiocytic lymphomas reveal cellular lineage, molecular defects, and sites of chromosomal translocation

Siminovitch, KA; Jensen, JP; Epstein, AL; Korsmeyer, SJ

doi:10.1182/blood.v67.2.391.bloodjournal672391

Cited by 4 publications

(4 citation statements)

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“…Previous gene expression profiles of diffuse large B‐cell lymphoma (DLBCL) cell lines demonstrated that both cell lines display similar molecular signatures, and cluster together with a ‘germinal centre‐derived’ phenotype rather than an ‘activated B‐cell type’ or ‘type3’ phenotype (Rosenwald et al , 2002). Both cell lines also carry the t(14;18) translocation involving the immunoglobulin heavy chain locus and bcl‐2 (Bakhshi et al , 1985; Siminovitch et al , 1986). SUDHL‐4 and SUDHL‐6 cell lines therefore represent a good model system to identify markers that account for their differential response to proteasome inhibition.…”

Section: Discussionmentioning

confidence: 99%

Gene expression analysis of B‐lymphoma cells resistant and sensitive to bortezomib*

et al. 2006

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Summary The proteasome inhibitor bortezomib has shown impressive clinical activity alone and in combination with conventional and other novel agents for the treatment of multiple myeloma (MM). Although bortezomib is known to be a selective proteasome inhibitor, the downstream mechanisms of cytotoxicity and drug resistance are poorly understood. However, resistance to bortezomib as a single agent develops in the majority of patients, and activity in other malignancies has been less impressive. To elucidate mechanisms of bortezomib resistance, we compared differential gene expression profiles of bortezomib‐resistant SUDHL‐4 and bortezomib‐sensitive SUDHL‐6 diffuse large B‐cell lymphoma lines in response to bortezomib. At concentrations that effectively inhibited proteasome activity, bortezomib induced apoptosis in SUDHL‐6 cells, but not in SUDHL‐4 cells. We showed that overexpression of activating transcription factor 3 (ATF3), ATF4, ATF5, c‐Jun, JunD and caspase‐3 is associated with sensitivity to bortezomib‐induced apoptosis, whereas overexpression of heat shock protein (HSP)27, HSP70, HSP90 and T‐cell factor 4 is associated with bortezomib resistance.

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Section: Discussionmentioning

confidence: 99%

Gene expression analysis of B‐lymphoma cells resistant and sensitive to bortezomib*

et al. 2006

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“…The involvement of the pseudo-JH3 gene in case 7 may be an example of inactivation of one IgH allele by t (14 ;18) and the other by nonfunctional rearrangement leading to defective Ig production . Indications for defects in transcription were given by Siminovitch et al (15), who described several diffuse B cell lymphoma cell lines without Ig H chain expression, in which one or both H chain alleles were rearranged . Truncated Ig H and L chain mRNAs were seen on Northern blots in one case, suggesting transcriptional defects (15).…”

Section: Discussionmentioning

confidence: 99%

“…Indications for defects in transcription were given by Siminovitch et al (15), who described several diffuse B cell lymphoma cell lines without Ig H chain expression, in which one or both H chain alleles were rearranged . Truncated Ig H and L chain mRNAs were seen on Northern blots in one case, suggesting transcriptional defects (15). The contribution ofother possible mechanisms in defective Ig production may be revealed by cloning and sequencing of IgH alleles in Igtumors and needs further research .…”

Section: Discussionmentioning

confidence: 99%

Translocation t(14;18) in B cell lymphomas as a cause for defective immunoglobulin production.

Jong¹,

Voetdijk²,

Ommen³

et al. 1989

The Journal of Experimental Medicine

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Although follicle center cell (FCC) lymphomas represent mature B cells, a considerable percentage do not have detectable Ig production. We have used Southern blotting and the polymerase chain reaction (PCR) to study the involvement of translocations t(14;18) and t(8;14) in causing defective Ig production in 16 Ig- FCC-derived lymphomas and three Ig- B cell acute lymphoblastic leukemias. In 6 of 19 cases, a t(14;18) was present with the other allele either deleted or in germline. In two cases a t(14;18) and a t(8;14) affected both Ig alleles, as confirmed by karyotyping. In two other cases, rearrangement of both bcl-2 on chromosome 18 and c-myc on chromosome 8 were found as well. Although cytogenetic proof was not available, the latter was probably involved in t(8;14). Restriction map analysis of one more case showed rearrangement on the pseudo-JH3 gene on one allele and t(14;18) on the other. Thus, in 11 of 19 cases, defective Ig H chain production could be explained by the inactivation of both Ig H chain genes due to translocation of one allele, in combination with deletions or defective rearrangements of the other allele. In contrast, in 28 of 30 Ig+ lymphomas, one functional Ig H chain allele was found, either in, or not in, combination with t(14;18). In two cases a single rearranged Ig H chain allele was found in combination with rearrangement of bcl-2. No comigration of the single Ig rearrangement with bcl-2, however, was found both by Southern blotting and PCR, suggesting a variant bcl-2 translocation, which leaves the Ig H chain allele functionally intact.

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“…The human DLBCL cell lines, OCI‐LY1 and SU‐DHL‐2, were available in our laboratory in SYSUCC. The cell lines were cultured in RPMI 1640 medium with 10% EV‐free fetal bovine serum (FBS) and 1% Pen‐Strep at 37°C under 5% CO 2 (RPMI 1640, FBS and Pen‐Strep were from Gibco).…”

Section: Methodsmentioning

confidence: 99%

Diffuse large B cell lymphoma‐derived extracellular vesicles educate macrophages to promote tumours progression by increasing PGC‐1β

et al. 2019

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Tumour-associated macrophages (TAMs) comprise an important part of the tumour microenvironment and play a key role in malignant tumours progression. Tumourderived extracellular vesicles (EVs) modulated TAMs polarization and reprogrammed TAMs to influence the progression of various tumours. Here, we hypothesized that diffuse large B cell lymphoma (DLBCL)-derived EVs can regulate macrophages polarization and thus contribute to tumour progression. Our results demonstrated that EVs, released from DLBCL, augment the M2 polarization effects of macrophages. Moreover, conditional medium derived from macrophages by DLBCL-derived EVs stimulation revealed the superior effects of promoting tumour proliferation, migration and invasion. Further analysis demonstrated that DLBCL-derived EVs regulated the metabolism of macrophages by increasing the expression of PGC-1β protein, therebyreprogramming the macrophage phenotype of promoting tumour progression. In conclusion, our findings signify that the DLBCL-derived EVs mediated the increasing of functional PGC-1β protein in macrophages to promote the tumour progression. SUPPORTING INFORMATIONAdditional supporting information may be found online in the Supporting Information section.How to cite this article: Liu W, Zhu M, Wang H, Wang W, Lu Y. Diffuse large B cell lymphoma-derived extracellular vesicles educate macrophages to promote tumours progression by increasing PGC-1β. Scand J Immunol. 2020;91:e12841. https ://doi.

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Immunoglobulin gene rearrangements and expression in diffuse histiocytic lymphomas reveal cellular lineage, molecular defects, and sites of chromosomal translocation

Cited by 4 publications

References 0 publications

Gene expression analysis of B‐lymphoma cells resistant and sensitive to bortezomib*

Gene expression analysis of B‐lymphoma cells resistant and sensitive to bortezomib*

Translocation t(14;18) in B cell lymphomas as a cause for defective immunoglobulin production.

Diffuse large B cell lymphoma‐derived extracellular vesicles educate macrophages to promote tumours progression by increasing PGC‐1β

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