Evidence map›Paper›PMID 31288832›Full record

ArticleJournal of hematology & oncology2019

Targeting MYC activity in double-hit lymphoma with MYC and BCL2 and/or BCL6 rearrangements with epigenetic bromodomain inhibitors.

Weiping Li, Shiv K Gupta, Weiguo Han, Ryan A Kundson, Sara Nelson, Darlene Knutson, Patricia T Greipp, Sherine F Elsawa, Eduardo M Sotomayor, Mamta Gupta

Abstract read
In one paragraph

Article in Journal of hematology & oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.

0numbers the graph read from it
0cells of the map it votes in
71citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

71 citing papers in PubMed.

  1. Review
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  12. Clinical scoring systems, molecular subtypes and baseline [Cancer imaging : the official publication of the International Cancer Imaging Society · 2024
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  13. Review
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  15. Article
  16. Deciphering the role of CD47 in cancer immunotherapy.Journal of advanced research · 2024
    Review
  17. Article
  18. Expanded profiling of WD repeat domain 5 inhibitors reveals actionable strategies for the treatment of hematologic malignancies.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  19. Article
  20. International journal of molecular sciences · 2024
    Article

11 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Weiping LiDepartment of Hematology, Mayo Clinic, Rochester, MN, USA.
Shiv K GuptaDepartment of Radiation Oncology, Mayo Clinic, Rochester, MN, USA.
Weiguo HanDepartment of Molecular, Cellular and Biomedical Sciences, University of New Hampshire, Durham, NH, USA.
Ryan A KundsonDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
Sara NelsonDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
Darlene KnutsonDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
Patricia T GreippDepartment of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
Sherine F ElsawaDepartment of Molecular, Cellular and Biomedical Sciences, University of New Hampshire, Durham, NH, USA.
Eduardo M SotomayorDepartment of Biochemistry and Molecular Medicine, School of Medicine and Health Sciences, George Washington University, GW Cancer Center, Washington, DC, 20052, USA.
Mamta GuptaDepartment of Hematology, Mayo Clinic, Rochester, MN, USA. magupta@gwu.edu.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Double/triple-hit lymphomas (DHL/THL) account for 5-10% of diffuse large B cell lymphoma (DLBCL) with rearrangement of MYC and BCL2 and/or BCL6 resulting in MYC overexpression. Despite the poor prognosis of DHL, R-CHOP chemotherapy remains the treatment backbone and new targeted therapy is needed. We performed comprehensive cytogenetic studies/fluorescence in situ hybridization on DLBCL and Burkitt lymphoma cell lines (n = 11) to identify the DHL/THL DLBCL in vitro model. We identified MYC/IG in Raji and Ramos (single hit); MYC/IG-BCL2 (DHL) in DOHH2, OCI-LY1, SUDHL2, and OCI-LY10; MYC/IG-BCL2/BCL6 (THL) in VAL; and no MYC rearrangement in U2932 and HBL1 (WT-MYC). Targeting MYC in the DHL/THL DLBCLs through bromodomain extra-terminal inhibitors (BETi) (JQ1, I-BET, and OTX015) significantly (p < 0.05) reduced proliferation, similar to WT-MYC cells, accompanied by decreased MYC but not BCL2 protein. Moreover, BETi suppressed MYC transcription and decreased BRD4 binding to MYC promoter in DHL cells. CD47 and PD-L1 are immunoregulatory molecules often expressed on tumors and regulated by MYC. High levels of surface CD47 but not surface PD-L1 was observed in DHL/THL, which was reduced by JQ1 treatment. BETi in combination with Pan-HDAC inhibitor had a limited effect on survival of DHL/THL, while combination of BETi and BCL2 inhibitor (ABT-199) had a significant (p < 0.005) inhibitory effect on survival followed by BCL-XL inhibition. Overall, the data suggests that MYC-expressing DLBCLs are probably addicted to the MYC-oncogenic effect regardless of MYC rearrangements. In summary, we identified an in vitro model for DHL/THL DLBCLs and provide evidence for the therapeutic potential of BET inhibitor alone or in combination with BCL2 inhibitor.

Indexed as

Cell Line, TumorCell ProliferationCell SurvivalFemaleHumansLymphoma, Large B-Cell, DiffuseMaleProto-Oncogene Proteins c-bcl-2Proto-Oncogene Proteins c-bcl-6Proto-Oncogene Proteins c-mycTransfectionBCL2 protein, humanBCL6 protein, humanProto-Oncogene Proteins c-bcl-2Proto-Oncogene Proteins c-bcl-6Proto-Oncogene Proteins c-mycBCL2BET bromodomainBRD4DLBCLDouble-hit lymphomaMYC

Identifiers

PMID31288832
PMCPMC6617630

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.