Evidence map›Paper›PMID 29746793›Full record

ArticleSLAS discovery : advancing life sciences R & D2018

High-Throughput Flow Cytometry Identifies Small-Molecule Inhibitors for Drug Repurposing in T-ALL.

Dominique R Perez, Christian K Nickl, Anna Waller, Cristina Delgado-Martin, Travis Woods, Nitesh D Sharma, Michelle L Hermiston, Mignon L Loh, Stephen P Hunger, Stuart S Winter and 4 more

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

Article in SLAS discovery : advancing life sciences R & D, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.9field-weighted citation impact, top 22% 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

3 citing papers in PubMed, 8 citations in OpenAlex.

  1. Article
  2. Review
  3. 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

14 authors at 7 institutions in 1 country.

Dominique R Perez1 Department of Pathology, Health Sciences Center, University of New Mexico, Albuquerque, NM, USA.
Christian K Nickl3 University of New Mexico Comprehensive Cancer Center, Albuquerque, NM, USA.
Anna Waller1 Department of Pathology, Health Sciences Center, University of New Mexico, Albuquerque, NM, USA.
Cristina Delgado-Martin5 Department of Pediatrics, Benioff Children's Hospital, University of California, San Francisco, CA, USA.
Travis Woods1 Department of Pathology, Health Sciences Center, University of New Mexico, Albuquerque, NM, USA.
Nitesh D Sharma3 University of New Mexico Comprehensive Cancer Center, Albuquerque, NM, USA.
Michelle L Hermiston5 Department of Pediatrics, Benioff Children's Hospital, University of California, San Francisco, CA, USA.
Mignon L Loh5 Department of Pediatrics, Benioff Children's Hospital, University of California, San Francisco, CA, USA.
Stephen P Hunger6 Department of Pediatrics and the Center for Childhood Cancer Research, Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Stuart S Winter7 Children's Minnesota Research Institute, Children's Minnesota, Minneapolis, MN, USA.
Alexandre Chigaev1 Department of Pathology, Health Sciences Center, University of New Mexico, Albuquerque, NM, USA.
Bruce Edwards1 Department of Pathology, Health Sciences Center, University of New Mexico, Albuquerque, NM, USA.
Larry A Sklar1 Department of Pathology, Health Sciences Center, University of New Mexico, Albuquerque, NM, USA.
Ksenia Matlawska-Wasowska3 University of New Mexico Comprehensive Cancer Center, Albuquerque, NM, USA.
UNM Comprehensive Cancer CenterNew Mexico Cancer Center · USUniversity of California, San Francisco · USUniversity of New Mexico · USChildren's Hospital of Philadelphia · USChildren’s Institute · USUCSF Benioff Children's Hospital · US

Funding

WOMEN'S CANCERS RESEARCH PROGRAMP30CA118100 · NCI · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · PI Yolanda Sanchez · 2005 to 2026
$57.1M
UNM HSC Clinical and Translational Science CenterUL1TR001449 · NCATS · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · PI CAMPEN, MATTHEW J, PANDHI, NANCY · 2015 to 2024
$36.9M
University of New Mexico Clinical and Translational Science CenterUL1TR000041 · NCATS · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · PI LARSON, RICHARD S · 2012 to 2014
$9.8M
MINORITY INSTITUTIONAL RESEARCH TRAINING PROGRAM (T32)T32HL007736 · NHLBI · UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR · PI RESTA, THOMAS C · 1993 to 2025
$6.5M
Multiplex Screening for ABC Transporter InhibitorsR03MH081228 · NIMH · UNIVERSITY OF NEW MEXICO · PI LARSON, RICHARD S · 2007 to 2007
$25k
NCATS NIH HHS UL1 TR000041NCATS NIH HHS UL1 TR001449NCI NIH HHS P30 CA118100NHLBI NIH HHS T32 HL007736NIMH NIH HHS R03 MH081228
6 · The paper itself

Abstract

Kinase inhibitors have dramatically increased patient survival in a multitude of cancers, including hematological malignancies. However, kinase inhibitors have not yet been integrated into current clinical trials for patients with T-cell-lineage acute lymphoblastic leukemia (T-ALL). In this study, we used a high-throughput flow cytometry (HTFC) approach to test a collection of small-molecule inhibitors, including 26 FDA-approved tyrosine kinase inhibitors in a panel of T-ALL cell lines and patient-derived xenografts. Because hypoxia is known to cause resistance to chemotherapy, we developed a synthetic niche that mimics the low oxygen levels found in leukemic bone marrow to evaluate the effects of hypoxia on the tested inhibitors. Drug sensitivity screening was performed using the Agilent BioCel automated liquid handling system integrated with the HyperCyt HT flow cytometry platform, and the uptake of propidium iodide was used as an indication of cell viability. The HTFC dose-response testing identified several compounds that were efficacious in both normal and hypoxic conditions. This study shows that some clinically approved kinase inhibitors target T-ALL in the hypoxic niche of the bone marrow.

Indexed as

Drug DiscoveryDrug RepositioningFlow CytometryHigh-Throughput Screening AssaysSmall Molecule LibrariesAnimalsAntineoplastic AgentsCell Line, TumorDose-Response Relationship, DrugHumansMicePrecursor T-Cell Lymphoblastic Leukemia-LymphomaProtein Kinase InhibitorsAntineoplastic AgentsProtein Kinase InhibitorsSmall Molecule Librarieshigh-throughput screeninghypoxiakinase inhibitorsleukemiaT-ALL

Identifiers

PMID29746793
PMCPMC6292518
OpenAlexW2802932286

What OpenQuestion holds

Textmetadata
LicenceTDM
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.