Evidence map›Paper›PMID 39105568›Full record

ArticleBlood cancer discovery2024

Repurposing NAMPT Inhibitors for Germinal Center B Cell-Like Diffuse Large B-Cell Lymphoma.

Claudio Scuoppo, Bowen Cai, Kenneth Ofori, Hanna Scholze, Rahul Kumar, Angelo D'Alessandro, Katia Basso, Laura Pasqualucci, Riccardo Dalla-Favera

Abstract read
In one paragraph

Article in Blood cancer discovery, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. Article
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

9 authors.

Claudio ScuoppoInstitute for Cancer Genetics, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York.ORCID 0000-0003-4615-0883
Bowen CaiInstitute for Cancer Genetics, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York.ORCID 0009-0000-7995-4920
Kenneth OforiInstitute for Cancer Genetics, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York.ORCID 0000-0002-4422-2882
Hanna ScholzeInstitute for Cancer Genetics, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York.ORCID 0000-0003-1006-8191
Rahul KumarInstitute for Cancer Genetics, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York.ORCID 0000-0002-6927-5390
Angelo D'AlessandroDepartment of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, Colorado.ORCID 0000-0002-2258-6490
Katia BassoInstitute for Cancer Genetics, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York.ORCID 0000-0002-9316-6039
Laura PasqualucciInstitute for Cancer Genetics, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York.ORCID 0000-0001-6819-7370
Riccardo Dalla-FaveraInstitute for Cancer Genetics, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York.ORCID 0000-0002-3502-8826

Funding

Tumor Biology and Microenvironment ProgramP30CA013696 · NCI · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI Anil K Rustgi · 1985 to 2026
$115.3M
Translating Stress Response Targeted Therapy for B-Cell LymphomasP50CA192937 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI DALLA-FAVERA, RICCARDO, ZELENETZ, ANDREW D. · 2016 to 2020
$10.9M
From pathogenesis to new therapeutic targets in Diffuse Large B cell LymphomaR35CA210105 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Riccardo Dalla-Favera · 2016 to 2026
$10.0M
BD Biosciences InfluxS10OD020056 · OD · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI SNOECK, HANS-WILLEM E · 2015 to 2015
$600k
American Society of Hematology (ASH) Restart AwardLeukemia and Lymphoma Society (LLS) TRP 6644-22National Cancer Institute (NCI) P50CA-192937National Cancer Institute (NCI) R35CA-210105National Institutes of Health (NIH) S10OD020056NCI NIH HHS P30 CA013696NCI NIH HHS P50 CA192937NCI NIH HHS R35 CA210105NIH HHS S10 OD020056
6 · The paper itself

Abstract

Diffuse large B-cell lymphoma (DLBCL) includes the activated B cell-like (ABC) and germinal center B cell-like (GCB) subtypes, which differ in cell of origin, genetics, and clinical response. By screening the subtype-specific activity of 211 drugs approved or in active clinical development for other diseases, we identified inhibitors of nicotinamide phosphoribosyl transferase (NAMPTi) as active in a subset of GCB-DLBCL in vitro and in vivo. We validated three chemically distinct NAMPTis for their on-target activity based on biochemical and genetic rescue approaches and found the ratio between NAMPT and PARP1 RNA levels was predictive of NAMPTi sensitivity across DLBCL subtypes. Notably, the NAMPT:PARP1 transcript ratio predicts higher antitumor activity in BCL2-translocated GCB-DLBCL. Accordingly, pharmacologic and genetic inhibition of BCL2 was potently synergistic with NAMPT blockade. These data support the inhibition of NAMPT as a therapeutically relevant strategy for BCL2-translocated DLBCLs. Significance: Targeted therapies have emerged for the ABC subtype of DLBCL, but not for the GCB subtype, despite the evidence of a significant subset of high-risk cases. We identify a drug that specifically targets a subset of GCB-DLBCL and provide preclinical evidence for BCL2 translocations as biomarkers for their identification.

Indexed as

CytokinesLymphoma, Large B-Cell, DiffuseNicotinamide PhosphoribosyltransferaseAnimalsAntineoplastic AgentsCell Line, TumorDrug RepositioningGerminal CenterHumansMiceXenograft Model Antitumor AssaysAntineoplastic AgentsCytokinesNicotinamide Phosphoribosyltransferasenicotinamide phosphoribosyltransferase, human

Identifiers

PMID39105568
PMCPMC11528193

What OpenQuestion holds

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Registered trials

None linked

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.