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Genetic lesions in MYC and STAT3 drive oncogenic transcription factor overexpression in plasmablastic lymphoma

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dc.contributor.author García Reyero, Júlia
dc.contributor.author Martínez Magunacelaya, Nerea
dc.contributor.author González de Villambrosía, Sonia
dc.contributor.author Loghavi, Sanam
dc.contributor.author Gómez Mediavilla, Ángela
dc.contributor.author Tonda, Raúl
dc.contributor.author Beltran, Sergi
dc.contributor.author Gut, Marta
dc.contributor.author Pereña González, Ainara
dc.contributor.author d'Ámore, Emanuele
dc.contributor.author Visco, Carlo
dc.contributor.author Khoury, Joseph D.
dc.contributor.author Montes-Moreno, Santiago
dc.date.accessioned 2020-11-11T10:47:56Z
dc.date.available 2020-11-11T10:47:56Z
dc.date.issued 2020
dc.identifier.citation Garcia-Reyero J, Martinez Magunacelaya N, Gonzalez de Villambrosia S, Loghavi S, Gomez Mediavilla A, Tonda R, Beltran S, Gut M, Pereña Gonzalez A, d' Ámore E, Visco C, Khoury JD, Montes-Moreno S. Genetic lesions in MYC and STAT3 drive oncogenic transcription factor overexpression in plasmablastic lymphoma. Haematologica. 2020 Apr 9;106(4):1120-28. DOI: 10.3324/haematol.2020.251579
dc.identifier.issn 0390-6078
dc.identifier.uri http://hdl.handle.net/10230/45721
dc.description.abstract Plasmablastic lymphoma mutational profile is undescribed. Here we performed a targeted exonic NGS analysis of 30 plasmablastic lymphoma cases with a B cell lymphoma dedicated panel and FISH for the detection of MYC rearrangements. A complete phenotyping of the neoplastic and microenvironment cell populations was also performed. We have identified an enrichment in recurrent genetic events in MYC (69% with MYC translocation or amplification and 3 cases with missense point mutations), PRDM1/Blimp1 and STAT3 mutations. These gene mutations were more frequent in EBV positive disease. Other genetic events included mutations in BRAF, EP300, BCR (CD79A and CD79B), NOTCH pathway (NOTCH2, NOTCH1 and SGK1) and MYD88pL265P. Immunohistochemical analysis showed consistent MYC expression, higher in cases with MYC rearrangements together with phospho-STAT3 (Tyr705) overexpression in cases with STAT3 SH2 domain mutations. Microenvironment populations were heterogeneous and unrelated with EBV, with an enrichment of Tumor Associated Macrophages (TAM) and PD1 positive T cells. PD-L1 was expressed in all cases in the TAM population but only in 5 cases in the neoplastic cells (4 out of 14 EBV positive cases). HLA expression was absent in the majority of PBL cases. In summary, Plasmablastic lymphoma mutational profile is heterogeneous and related with EBV infection. Genetic events in MYC, STAT3 and PRDM1/Blimp1 are more frequent in EBV positive disease. An enrichment in TAM and PD1 reactive T lymphocytes is found in the microenvironment of PBL cases, that express PD-L1 in the neoplastic cells in a fraction of cases.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Ferrata Storti Foundation
dc.relation.ispartof Haematologica. 2020 Apr 9;106(4):1120-28
dc.rights © 2020 Ferrata Storti Foundation. Papers in Haematologica are published under a Creative Commons license CC BY-NC-ND. According to this license, an article may be copied, displayed, distributed, republished or otherwise reused provided the reuse is not an adaptation or a modification and the integrity of the original paper is maintained. This license does not allow for any kind of commercial use of the paper. For more details, see About Haematologica.
dc.rights.uri https://creativecommons.org/licenses/by/4.0/
dc.title Genetic lesions in MYC and STAT3 drive oncogenic transcription factor overexpression in plasmablastic lymphoma
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.3324/haematol.2020.251579
dc.subject.keyword Aggressive Non-Hodgkin's Lymphoma
dc.subject.keyword Immune microenvironment
dc.subject.keyword Oncogene activation
dc.subject.keyword Plasmablastic lymphoma
dc.subject.keyword Targeted NGS
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion

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