Gene expression analysis of plasmablastic lymphoma identifies downregulation of B-cell receptor signaling and additional unique transcriptional programs

Chapman, Jennifer R.; Gentles, Andrew J.; Sujoy, Victoria; Vega, Francisco; Dumur, Catherine I.; Blevins, Tana; Bernal‐Mizrachi, Leon; Mošunjac, Marina; Pimentel, Agustin; Zhu, Daxing

doi:10.1038/leu.2015.109

Cited by 41 publications

(31 citation statements)

References 25 publications

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“…This protein expression profile has been described extensively in previous papers 4 and confirms recently published data on the gene expression profile of plasmablastic lymphoma cases. 9 Furthermore, this protein expression profile is common to other B-cell lymphomas with immunoblastic/plasmablastic differentiation such as ALK+ large B-cell lymphoma. 12 However, other proteins found to be overexpressed in ALK+ large B-cell lymphoma such as STAT3-P 12 have only a limited expression in our plasmablastic lymphoma cases.…”

Section: Prdm1 Gene Is Recurrently Mutated In Plasmablastic Lymphoma mentioning

confidence: 96%

“…12 Gene expression analysis of plasmablastic lymphoma has found MYC overexpression at the mRNA level, and this overexpression is correlated with protein overexpression as detected by immunohistochemistry. 9 Interestingly MYC overeexpression as detected by immunohistochemistry seems not to be restricted to those cases with MYC translocation by fluorescent in situ hybridization. 12,13 All these data suggest that MYC overexpression has a central role in the pathogenesis of plasmablastic lymphoma.…”

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confidence: 94%

“…3,4,8 In addition, recent evidence suggests that EBV or HIV status does not influence the gene expression profile patterns of plasmablastic lymphoma. 9 Genetic alterations in MYC have been found in a proportion (~60%) of plasmablastic lymphoma cases, 10,11 mainly consisting of translocations involving MYC and Ig. These translocations are not found in other lymphoma types with immunoblastic/ plasmablastic phenotype such as ALK+ large B-cell lymphoma, that may show another cytogenetic alterations involving MYC but lack MYC translocations.…”

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confidence: 99%

“…4,16 Recently, gene expression profiling data support the notion that the plasma cell differentiation program in plasmablastic lymphoma cases is due, as in normal plasma cells, to downregulation of BCR genes, and upregulation of both Blimp1 and XBP1s. 9 Interestingly enough, in normal plasma cells, Blimp1, serves as a transcriptional repressor of MYC expression 17 and is able to induce apoptosis by MYC downregulation in different lymphoma cell lines. 17 Conversely, MYC protein is able to block terminal differentiation in several hematopoietic cell lines (cited in ref.…”

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confidence: 99%

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Plasmablastic lymphoma phenotype is determined by genetic alterations in MYC and PRDM1

et al. 2017

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Plasmablastic lymphoma is an uncommon aggressive non-Hodgkin B-cell lymphoma type defined as a high-grade large B-cell neoplasm with plasma cell phenotype. Genetic alterations in MYC have been found in a proportion (~60%) of plasmablastic lymphoma cases and lead to MYC-protein overexpression. Here, we performed a genetic and expression profile of 36 plasmablastic lymphoma cases and demonstrate that MYC overexpression is not restricted to MYC-translocated (46%) or MYC-amplified cases (11%). Furthermore, we demonstrate that recurrent somatic mutations in PRDM1 are found in 50% of plasmablastic lymphoma cases (8 of 16 cases evaluated). These mutations target critical functional domains (PR motif, proline rich domain, acidic region, and DNA-binding Zn-finger domain) involved in the regulation of different targets such as MYC. Furthermore, these mutations are found frequently in association with MYC translocations (5 out of 9, 56% of cases with MYC translocations were PRDM1-mutated), but not restricted to those cases, and lead to expression of an impaired PRDM1/Blimp1α protein. Our data suggest that PRDM1 mutations in plasmablastic lymphoma do not impair terminal B-cell differentiation, but contribute to the oncogenicity of MYC, usually disregulated by MYC translocation or MYC amplification. In conclusion, aberrant coexpression of MYC and PRDM1/Blimp1α owing to genetic changes is responsible for the phenotype of plasmablastic lymphoma cases.

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Section: Prdm1 Gene Is Recurrently Mutated In Plasmablastic Lymphoma mentioning

confidence: 96%

mentioning

confidence: 94%

mentioning

confidence: 99%

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confidence: 99%

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Plasmablastic lymphoma phenotype is determined by genetic alterations in MYC and PRDM1

et al. 2017

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“…[1] Recently, PBL is also identified as a subtype of non-Hodgkin lymphoma (NHL), and it is estimated incidence of PBL accounts for approximately 5% of all HIV-positive NHL cases. [2] Despite the strong relationship with HIV infection, PBL could also influence the HIV-negative patients.…”

Section: Introductionmentioning

confidence: 99%

Plasmablastic lymphoma

Han

Duan²,

Hu³

et al. 2017

Medicine

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Plasmablastic lymphoma: 2024 update on diagnosis, risk stratification, and management

Ramirez‐Gamero,

Martínez‐Cordero,

Beltrán

et al. 2024

American J Hematol

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Disease OverviewPlasmablastic lymphoma (PBL) is a rare CD20‐negative aggressive lymphoma with a poor prognosis under standard treatment options. Though PBL is associated with human immunodeficiency virus infection and other immunosuppressed states, it can also affect immunocompetent individuals.DiagnosisThe diagnosis requires a high clinical suspicion and pathological confirmation. EBER expression and MYC gene rearrangements are frequently detected. The differential diagnosis includes EBV+ diffuse large B‐cell lymphoma, extracavitary primary effusion lymphoma, ALK+ DLBCL, and HHV8+ large B‐cell lymphoma, among others.Risk StratificationAge ≥60 years, advanced clinical stage, and high intermediate and high International Prognostic Index scores are associated with worse survival.ManagementCombination chemotherapy regimens, such as EPOCH, are recommended. The addition of bortezomib, lenalidomide, or daratumumab might improve outcomes. Including PBL patients and their participation in prospective clinical trials is warranted.

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Gene expression analysis of plasmablastic lymphoma identifies downregulation of B-cell receptor signaling and additional unique transcriptional programs

Cited by 41 publications

References 25 publications

Plasmablastic lymphoma phenotype is determined by genetic alterations in MYC and PRDM1

Plasmablastic lymphoma phenotype is determined by genetic alterations in MYC and PRDM1

Plasmablastic lymphoma

Plasmablastic lymphoma: 2024 update on diagnosis, risk stratification, and management

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