Evidence map›Paper›PMID 24301524›Full record

ArticleLeukemia2014

Proteasome inhibitors exert cytotoxicity and increase chemosensitivity via transcriptional repression of Notch1 in T-cell acute lymphoblastic leukemia.

D Koyama, J Kikuchi, N Hiraoka, T Wada, H Kurosawa, S Chiba, Y Furukawa

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Leukemia, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed, 1 pooled it
2.1field-weighted citation impact, top 14% 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.

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

42 citing papers in PubMed, 1 synthesis or guideline pooled it, 65 citations in OpenAlex.

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  17. High-Risk Mantle Cell Lymphoma in the Era of Novel Agents.Current hematologic malignancy reports · 2021
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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

7 authors at 3 institutions in 1 country.

D KoyamaDivision of Stem Cell Regulation, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan.
J KikuchiDivision of Stem Cell Regulation, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan.
N HiraokaDivision of Stem Cell Regulation, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan.
T WadaDivision of Stem Cell Regulation, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan.
H KurosawaDepartment of Pediatrics, Dokkyo Medical University, School of Medicine, Tochigi, Japan.
S ChibaDepartment of Hematology and Tsukuba Advanced Research Alliance, University of Tsukuba, Ibaraki, Japan.
Y FurukawaDivision of Stem Cell Regulation, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan.
Jichi Medical University · JPDokkyo Medical University · JPUniversity of Tsukuba · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The Notch signaling pathway has been recognized as a key factor for the pathogenesis of T-cell acute lymphoblastic leukemia (T-ALL), because of the high incidence of activating mutations of Notch1. Notch inhibition could serve as a new treatment strategy for T-ALL; however, the attempts to perturb Notch signaling pathways have been unsuccessful so far. In this study, we found that proteasome inhibitors exert cytotoxic effects on T-ALL cells with constitutive activation of Notch1 to a similar extent as myeloma cells. The proteasome inhibitor bortezomib repressed the transcription of Notch1 and downstream effectors including Hes1, GATA3, RUNX3 and nuclear factor-κB (NF-κB) (p65 and p50), coincided with downregulation of the major transactivator Sp1 and its dissociation from Notch1 promoter. Overexpression of the Notch1 intracellular domain (NICD) significantly ameliorated bortezomib-induced cytotoxicity against T-ALL cells. Drug combination studies revealed that bortezomib showed synergistic or additive effects with key drugs for the treatment of T-ALL such as dexamethasone (DEX), doxorubicin and cyclophosphamide, which were readily abolished by NICD overexpression. The synergy of bortezomib and DEX was confirmed in vivo using a murine xenograft model. Our findings provide a molecular basis and rationale for the inclusion of proteasome inhibitors in treatment strategies for T-ALL.

Indexed as

AnimalsApoptosisBlotting, WesternBoronic AcidsBortezomibCell ProliferationChromatin ImmunoprecipitationCore Binding Factor Alpha 3 SubunitDrug Resistance, NeoplasmHumansMiceMice, Inbred NODMice, SCIDNF-kappa BPrecursor T-Cell Lymphoblastic Leukemia-LymphomaProteasome InhibitorsBoronic AcidsBortezomibCore Binding Factor Alpha 3 SubunitNF-kappa BProteasome InhibitorsPyrazinesReceptor, Notch1RNA, Messenger

Identifiers

PMID24301524
PMCPMC4051216
OpenAlexW2051121908

What OpenQuestion holds

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LicenceCC BY-NC-ND
Read underepoch 390

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.