Evidence map›Paper›PMID 22490804›Full record

ArticleBlood2012

Zebrafish screen identifies novel compound with selective toxicity against leukemia.

Suzanne Ridges, Will L Heaton, Deepa Joshi, Henry Choi, Anna Eiring, Lance Batchelor, Priya Choudhry, Elizabeth J Manos, Hossein Sofla, Ali Sanati and 16 more

Open access · bronzeAbstract read
In one paragraph

Article in Blood, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.

0numbers the graph read from it
0cells of the map it votes in
87citing papers in PubMed
5.6field-weighted citation impact, top 3% 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

87 citing papers in PubMed, 156 citations in OpenAlex.

  1. Review
  2. Zebrafish live imaging: a strong weapon in anticancer drug discovery and development.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024
    Review
  3. What value do zebrafish have to anticancer drug discovery?Expert opinion on drug discovery · 2024
    Article
  4. Review
  5. Review
  6. Review
  7. Learning from Zebrafish Hematopoiesis.Advances in experimental medicine and biology · 2023
    Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Zebrafish Xenograft Model to Study Human Cancer.Methods in molecular biology (Clifton, N.J.) · 2022
    Article
  14. Zebrafish models of acute leukemias: Current models and future directions.Wiley interdisciplinary reviews. Developmental biology · 2021
    Review
  15. Using the Zebrafish as a Genetic Model to Study Erythropoiesis.International journal of molecular sciences · 2021
    Review
  16. Review
  17. Zebrafish as a Model for Anticancer Nanomedicine Studies.Pharmaceuticals (Basel, Switzerland) · 2021
    Review
  18. Article
  19. Article
  20. Article

27 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

26 authors at 8 institutions in 2 countries.

Suzanne RidgesDepartment of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA.
Will L Heaton
Deepa Joshi
Henry Choi
Anna Eiring
Lance Batchelor
Priya Choudhry
Elizabeth J Manos
Hossein Sofla
Ali Sanati
Seth Welborn
Archana Agarwal
Gerald J Spangrude
Rodney R Miles
James E Cox
J Kimble Frazer
Michael Deininger
Kaveri Balan
Matthew Sigman
Markus Müschen
Tatiana Perova
Radia Johnson
Bertrand Montpellier
Cynthia J Guidos
David A Jones
Nikolaus S Trede
Huntsman Cancer Institute · USUniversity of Toronto · CAUniversity of Utah · USBiologie du Développement et Cellules SouchesHospital for Sick Children · CAJoint Center for Structural Genomics · USPediatrics and Genetics · USUniversity of Southern California · US

Funding

UTAH REGIONAL CANCER CENTERP30CA042014 · NCI · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI Jared P Rutter · 1986 to 2026
$72.6M
APC and Retinoids in Zebrafish Enterocyte DevelopmentR01CA116468 · NCI · UNIVERSITY OF UTAH · PI JONES, DAVID A · 2005 to 2020
$4.2M
PRE-B CELL RECEPTOR SIGNALING IN ACUTE LYMPHOBLASTIC LEUKEMIAR01CA137060 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MÜSCHEN, MARKUS · 2009 to 2016
$2.7M
NCI NIH HHS P30 CA042014NCI NIH HHS R01 CA116468NCI NIH HHS R01 CA137060
6 · The paper itself

Abstract

To detect targeted antileukemia agents we have designed a novel, high-content in vivo screen using genetically engineered, T-cell reporting zebrafish. We exploited the developmental similarities between normal and malignant T lymphoblasts to screen a small molecule library for activity against immature T cells with a simple visual readout in zebrafish larvae. After screening 26 400 molecules, we identified Lenaldekar (LDK), a compound that eliminates immature T cells in developing zebrafish without affecting the cell cycle in other cell types. LDK is well tolerated in vertebrates and induces long-term remission in adult zebrafish with cMYC-induced T-cell acute lymphoblastic leukemia (T-ALL). LDK causes dephosphorylation of members of the PI3 kinase/AKT/mTOR pathway and delays sensitive cells in late mitosis. Among human cancers, LDK selectively affects survival of hematopoietic malignancy lines and primary leukemias, including therapy-refractory B-ALL and chronic myelogenous leukemia samples, and inhibits growth of human T-ALL xenografts. This work demonstrates the utility of our method using zebrafish for antineoplastic candidate drug identification and suggests a new approach for targeted leukemia therapy. Although our efforts focused on leukemia therapy, this screening approach has broad implications as it can be translated to other cancer types involving malignant degeneration of developmentally arrested cells.

Indexed as

AnimalsAntineoplastic AgentsApoptosisBlast CrisisCell DifferentiationDisease Models, AnimalDisease ProgressionHumansHydrazonesLeukemiaMiceMitosisPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsPhosphorylationPrecursor T-Cell Lymphoblastic Leukemia-Lymphoma1H-indole-3-carbaldehyde quinolin-8-yl-hydrazoneAntineoplastic AgentsHydrazonesPhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsProto-Oncogene Proteins c-aktQuinolinesTOR Serine-Threonine Kinases

Identifiers

PMID22490804
PMCPMC3382926
OpenAlexW1987558337

What OpenQuestion holds

Textmetadata
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.