Evidence map›Paper›PMID 24161946›Full record

ArticleNature chemical biology2013

Niche-based screening identifies small-molecule inhibitors of leukemia stem cells.

Kimberly A Hartwell, Peter G Miller, Siddhartha Mukherjee, Alissa R Kahn, Alison L Stewart, David J Logan, Joseph M Negri, Mildred Duvet, Marcus Järås, Rishi Puram and 27 more

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

Article in Nature chemical biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.

0numbers the graph read from it
0cells of the map it votes in
68citing papers in PubMed
7.4field-weighted citation impact, top 2% 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

68 citing papers in PubMed, 109 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Review
  8. Review
  9. Review
  10. Review
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Review
  17. Article
  18. Article
  19. Article
  20. Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

37 authors at 7 institutions in 1 country.

Kimberly A Hartwell *Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Peter G Miller *Division of Hematology, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Siddhartha MukherjeeCenter for Regenerative Medicine and Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.
Alissa R KahnDepartment of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Alison L StewartBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
David J LoganBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Joseph M NegriBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Mildred DuvetBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Marcus JäråsDivision of Hematology, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Rishi PuramDivision of Hematology, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Vlado DancikBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Fatima Al-ShahrourBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Thomas KindlerDivision of Hematology, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Zuzana TothovaDivision of Hematology, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Shrikanta ChattopadhyayBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Thomas HasakaBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Rajiv NarayanBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Mingji DaiBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Christina HuangBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Sebastian ShterentalDivision of Hematology, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Lisa P ChuDivision of Hematology, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
J Erika HayduDivision of Hematology, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Jae Hung ShiehDepartment of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
David P SteensmaHarvard Medical School, Boston, MA 02115, USA.
Benito MunozBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Joshua A BittkerBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Alykhan F ShamjiBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Paul A ClemonsBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Nicola J TollidayBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Anne E CarpenterBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
D Gary GillilandBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Andrew M SternBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Malcolm A S MooreCell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
David T ScaddenBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Stuart L SchreiberBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Benjamin L EbertBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Todd R GolubBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Broad Institute · USHarvard University · USBrigham and Women's Hospital · USMemorial Sloan Kettering Cancer Center · USDana-Farber Cancer Institute · USHoward Hughes Medical Institute · USMassachusetts General Hospital · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4M
Medical Scientist Training ProgramT32GM007753 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI WALENSKY, LOREN DAVID · 1985 to 2021
$50.0M
Signatures of Kinase Activation in Cancer (MIT consortium)U54CA112962 · NCI · DANA-FARBER CANCER INSTITUTE · PI GOLUB, TODD R. · 2004 to 2014
$24.2M
Physician Scientist Training in Cancer ResearchT32CA009172 · NCI · DANA-FARBER CANCER INSTITUTE · PI Jennifer R Brown, James A. DeCaprio · 1985 to 2026
$17.1M
Discovery Pipeline (2 of 4)RL1CA133834 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI GOLUB, TODD R. · 2007 to 2011
$9.9M
TRAINING PROGRAM IN MOLECULAR HEMATOLOGYT32HL007623 · NHLBI · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI HANDIN, ROBERT I · 1985 to 2010
$7.0M
Driving Medical Projects (4 of 4)RL1GM084437 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI SCOLNICK, EDWARD MARK · 2007 to 2011
$5.9M
Target ID (3 of 4)RL1HG004671 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI SCHREIBER, STUART L · 2007 to 2011
$5.8M
Continued Development of CellProfiler Cell Image Analysis SoftwareR01GM089652 · NIGMS · BROAD INSTITUTE, INC. · PI CARPENTER, ANNE E. · 2010 to 2016
$3.7M
Targeting Metastasis Induced by Mesenchymal Stem Cells in the Tumor StromaK08CA158149 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI CHATTOPADHYAY, SHRIKANTA · 2011 to 2015
$890k
Genomics Based Drug DiscoveryUL1RR024924 · NCRR · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI SCOLNICK, EDWARD MARK · 2007 to 2007
$352k
PROXIMAL TUBULE NA/H EXCHANGE IN HYPERTENSIONF32HL010044 · NHLBI · UNIVERSITY OF IOWA · PI KEEN, HENRY L · 1998 to 2000
$38k
Howard Hughes Medical InstituteNCI NIH HHS K08 CA158149NCI NIH HHS N01 CO012400NCI NIH HHS P30 CA008748NCI NIH HHS RL1 CA133834NCI NIH HHS RL1CA133834NCI NIH HHS T32 CA009172NCI NIH HHS U54 CA112962NCI NIH HHS U54CA112962NCRR NIH HHS UL1 RR024924NCRR NIH HHS UL1RR024924NHGRI NIH HHS RL1 HG004671NHGRI NIH HHS RL1HG004671NHLBI NIH HHS T32 HL007623NHLBI NIH HHS U01HL1004402NIGMS NIH HHS R01 GM089652NIGMS NIH HHS RL1 GM084437NIGMS NIH HHS RL1GM084437NIGMS NIH HHS T32 GM007753
6 · The paper itself

Abstract

Efforts to develop more effective therapies for acute leukemia may benefit from high-throughput screening systems that reflect the complex physiology of the disease, including leukemia stem cells (LSCs) and supportive interactions with the bone marrow microenvironment. The therapeutic targeting of LSCs is challenging because LSCs are highly similar to normal hematopoietic stem and progenitor cells (HSPCs) and are protected by stromal cells in vivo. We screened 14,718 compounds in a leukemia-stroma co-culture system for inhibition of cobblestone formation, a cellular behavior associated with stem-cell function. Among those compounds that inhibited malignant cells but spared HSPCs was the cholesterol-lowering drug lovastatin. Lovastatin showed anti-LSC activity in vitro and in an in vivo bone marrow transplantation model. Mechanistic studies demonstrated that the effect was on target, via inhibition of HMG-CoA reductase. These results illustrate the power of merging physiologically relevant models with high-throughput screening.

Indexed as

LeukemiaAntineoplastic AgentsCell Line, TumorDrug Screening Assays, AntitumorHematopoietic Stem CellsHumansHydroxymethylglutaryl-CoA Reductase InhibitorsLovastatinNeoplastic Stem CellsAntineoplastic AgentsHydroxymethylglutaryl-CoA Reductase InhibitorsLovastatin

Identifiers

PMID24161946
PMCPMC4009363
OpenAlexW2081382204

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.