Evidence map›Paper›PMID 29396295›Full record

ArticleEBioMedicine2018

Metabolomic Profiling Reveals Cellular Reprogramming of B-Cell Lymphoma by a Lysine Deacetylase Inhibitor through the Choline Pathway.

Benet Pera, Jan Krumsiek, Sarit E Assouline, Rossella Marullo, Jayeshkumar Patel, Jude M Phillip, Lidia Román, Koren K Mann, Leandro Cerchietti

Registry-linked trialOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in EBioMedicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05834426 (Omic Technologies Applied to the Study of Diffuse Large B-cell Lymphoma and High-grade B-cell Lymphoma for the Discovery of Diagnostic and Prognosis Biomarkers), which is not on this map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
1.6field-weighted citation impact, top 17% of its field
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.

NCT05834426 not yet recruitingnot on this mapstarted 2023, after this paper: background citation

Omic Technologies Applied to the Study of Diffuse Large B-cell Lymphoma and High-grade B-cell Lymphoma for the Discovery of Diagnostic and Prognosis Biomarkers

TypeobservationalSponsorSociedad de Lucha Contra el Cáncer del EcuadorRan2023 to 2026Enrolled50ConditionsLymphoma, B-Cell, Neoplasms, Cancer, High-grade B-cell LymphomaArmsPlasma metabolomic profile by Ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-QTOFMS)
3 · Its place in the literature

Who cites it

22 citing papers in PubMed, 34 citations in OpenAlex.

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  20. Impact of post-surgical freezing delay on brain tumor metabolomics.Metabolomics : Official journal of the Metabolomic Society · 2019
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 3 countries.

Benet PeraHematology and Oncology Division, Weill Cornell Medicine, Cornell University, New York, NY, USA.
Jan KrumsiekHematology and Oncology Division, Weill Cornell Medicine, Cornell University, New York, NY, USA; Institute of Computational Biology, Helmholtz Zentrum München, Neuherberg, Germany.
Sarit E AssoulineSegal Cancer Center, Lady Davis Institute, Jewish General Hospital, McGill University, Montreal, QC, Canada.
Rossella MarulloHematology and Oncology Division, Weill Cornell Medicine, Cornell University, New York, NY, USA.
Jayeshkumar PatelHematology and Oncology Division, Weill Cornell Medicine, Cornell University, New York, NY, USA.
Jude M PhillipHematology and Oncology Division, Weill Cornell Medicine, Cornell University, New York, NY, USA.
Lidia RománHematology and Oncology Division, Weill Cornell Medicine, Cornell University, New York, NY, USA.
Koren K MannSegal Cancer Center, Lady Davis Institute, Jewish General Hospital, McGill University, Montreal, QC, Canada.
Leandro CerchiettiHematology and Oncology Division, Weill Cornell Medicine, Cornell University, New York, NY, USA. Electronic address: lec2010@med.cornell.edu.
Cornell University · USJewish General Hospital · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Despite the proven clinical antineoplastic activity of histone deacetylase inhibitors (HDACI), their effect has been reported to be lower than expected in B-cell lymphomas. Traditionally considered as "epigenetic drugs", HDACI modify the acetylation status of an extensive proteome, acting as general lysine deacetylase inhibitors (KDACI), and thus potentially impacting various branches of cellular metabolism. Here, we demonstrate through metabolomic profiling of patient plasma and cell lines that the KDACI panobinostat alters lipid metabolism and downstream survival signaling in diffuse large B-cell lymphomas (DLBCL). Specifically, panobinostat induces metabolic adaptations resulting in newly acquired dependency on the choline pathway and activation of PI3K signaling. This metabolic reprogramming decreased the antineoplastic effect of panobinostat. Conversely, inhibition of these metabolic adaptations resulted in superior anti-lymphoma effect as demonstrated by the combination of panobinostat with a choline pathway inhibitor. In conclusion, our study demonstrates the power of metabolomics in identifying unknown effects of KDACI, and emphasizes the need for a better understanding of these drugs in order to achieve successful clinical implementation.

Indexed as

Cellular ReprogrammingAnimalsCell Line, TumorCholineCholine KinaseHistone Deacetylase InhibitorsHumansHydroxamic AcidsIndolesLymphoma, Large B-Cell, DiffuseLysineMaleMetabolomeMetabolomicsMiceMorpholinesCHKA protein, humanCholineCholine KinaseCUDC-907Histone Deacetylase InhibitorsHydroxamic AcidsIndolesLysineMorpholinesPanobinostatPyrimidinesCholine pathwayDLBCLMetabolomicsPanobinostatPI3K

Identifiers

PMID29396295
PMCPMC5835559
OpenAlexW2789912283

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

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.