Evidence map›Paper›PMID 38406263›Full record

ArticleNAR cancer2024

SAMHD1 expression contributes to doxorubicin resistance and predicts survival outcomes in diffuse large B-cell lymphoma patients.

Waaqo Daddacha, Dominique Monroe, Ashley J Schlafstein, Allison E Withers, Elizabeth B Thompson, Diana Danelia, Nho C Luong, Fatmata Sesay, Sandip K Rath, Edidiong R Usoro and 15 more

Open access · goldAbstract read
In one paragraph

Article in NAR cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.8field-weighted citation impact, top 30% 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

5 citing papers in PubMed, 2 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Review
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

25 authors at 2 institutions in 1 country.

Waaqo DaddachaDepartment of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA.ORCID 0000-0003-1197-0742
Dominique MonroeDepartment of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA.ORCID 0000-0001-5714-2518
Ashley J SchlafsteinDepartment of Radiation Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Allison E WithersDepartment of Radiation Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Elizabeth B ThompsonDepartment of Radiation Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Diana DaneliaDepartment of Radiation Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Nho C LuongDepartment of Radiation Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Fatmata SesayDepartment of Radiation Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Sandip K RathDepartment of Radiation Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Edidiong R UsoroDepartment of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA.
Mark E EssienDepartment of Radiation Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Andrew T JungDepartment of Radiation Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Jinmeng G JiangDepartment of Radiation Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Jiaxuan HuDepartment of Radiation Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Bijan MahboubiDepartment of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA.
Arilyn WilliamsDepartment of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA.
Julia E SteinbeckDepartment of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA.
Xiaofeng YangDepartment of Radiation Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Zachary S BuchwaldDepartment of Radiation Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA.
William S DynanDepartment of Radiation Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA.ORCID 0000-0002-4045-5662
Jeffrey M SwitchenkoDepartment of Biostatistics and Bioinformatics, Rollins School of Public Health and Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322, USA.
Baek KimDepartment of Pediatrics, Emory University School of Medicine, Atlanta, GA 30322, USA.ORCID 0000-0001-7986-4335
Mohammad K KhanDepartment of Radiation Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA.
David L JayeDepartment of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
David S YuDepartment of Radiation Oncology, Emory University School of Medicine, Atlanta, GA 30322, USA.ORCID 0000-0002-2781-5379
Emory University · USAugusta University · US

Funding

Translational and Clinical Trial Correlates CoreU54CA274513 · NCI · CLEVELAND CLINIC LERNER COM-CWRU · PI Timothy An-thy Chan · 2022 to 2026
$9.3M
Lentivirus Replication Strategy and PathogenesisR01AI136581 · NIAID · EMORY UNIVERSITY · PI Baek Kim · 2018 to 2026
$3.9M
Mechanisms of SIRT2 Function in the Replication Stress ResponseR01CA178999 · NCI · EMORY UNIVERSITY · PI YU, DAVID SUNG-WEN · 2013 to 2023
$3.5M
Elucidating SAMHD1 in DNA Double-Strand Break Repair (Supplement)R01CA254403 · NCI · EMORY UNIVERSITY · PI KIM, BAEK, YU, DAVID SUNG-WEN · 2020 to 2024
$2.9M
SAMHD1 mediated dNTP regulation and HIV in myeloid cellsR01AI162633 · NIAID · EMORY UNIVERSITY · PI Baek Kim · 2021 to 2026
$2.7M
See, Reach, Treat Tumor-Optimized Transarterial Chemoembolization DrugDeliveryR01CA160771 · NCI · YALE UNIVERSITY · PI GESCHWIND, JEAN-FRANCOIS H, LIN, MINGDE · 2011 to 2015
$2.6M
Understanding mechanistic role of SAMHD1 in DNA damage response and therapeutic benefit for malignant gliomaK01CA226346 · NCI · EMORY UNIVERSITY · PI DADDACHA, WAAQO BORU · 2018 to 2022
$549k
NCI NIH HHS K01 CA226346NCI NIH HHS R01 CA160771NCI NIH HHS R01 CA178999NCI NIH HHS R01CA178999S1NCI NIH HHS R01 CA254403NCI NIH HHS U54 CA274513NIAID NIH HHS R01 AI136581NIAID NIH HHS R01 AI162633
6 · The paper itself

Abstract

Diffuse large B-cell lymphoma (DLBCL) is a commonly diagnosed, aggressive non-Hodgkin's lymphoma. While R-CHOP chemoimmunotherapy is potentially curative, about 40% of DLBCL patients will fail, highlighting the need to identify biomarkers to optimize management. SAMHD1 has a dNTPase-independent role in promoting resection to facilitate DNA double-strand break (DSB) repair by homologous recombination. We evaluated the relationship of SAMHD1 levels with sensitivity to DSB-sensitizing agents in DLBCL cells and the association of SAMHD1 expression with clinical outcomes in 79 DLBCL patients treated with definitive therapy and an independent cohort dataset of 234 DLBCL patients. Low SAMHD1 expression, Vpx-mediated, or siRNA-mediated degradation/depletion in DLBCL cells was associated with greater sensitivity to doxorubicin and PARP inhibitors. On Kaplan-Meier log-rank survival analysis, low SAMHD1 expression was associated with improved overall survival (OS), which on subset analysis remained significant only in patients with advanced stage (III-IV) and moderate to high risk (2-5 International Prognostic Index (IPI)). The association of low SAMHD1 expression with improved OS remained significant on multivariate analysis independent of other adverse factors, including IPI, and was validated in an independent cohort. Our findings suggest that SAMHD1 expression mediates doxorubicin resistance and may be an important prognostic biomarker in advanced, higher-risk DLBCL patients.

Indexed as

DoxorubicinDrug Resistance, NeoplasmLymphoma, Large B-Cell, DiffuseSAM Domain and HD Domain-Containing Protein 1AdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorCell Line, TumorFemaleHumansKaplan-Meier EstimateMaleMiddle AgedPrognosisBiomarkers, TumorDoxorubicinSAM Domain and HD Domain-Containing Protein 1SAMHD1 protein, human

Identifiers

PMID38406263
PMCPMC10894040
OpenAlexW4392129222

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.