Evidence map›Paper›PMID 27058663›Full record

ArticleCell2016

Core Circadian Clock Genes Regulate Leukemia Stem Cells in AML.

Rishi V Puram, Monika S Kowalczyk, Carl G de Boer, Rebekka K Schneider, Peter G Miller, Marie McConkey, Zuzana Tothova, Héctor Tejero, Dirk Heckl, Marcus Järås and 8 more

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

Article in Cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 169 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
169citing papers in PubMed, 1 pooled it
13.6field-weighted citation impact, top 1% 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

169 citing papers in PubMed, 1 synthesis or guideline pooled it, 271 citations in OpenAlex.

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors at 7 institutions in 4 countries.

Rishi V PuramDepartment of Medicine, Division of Hematology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of Harvard University and MIT, Cambridge, MA 02142, USA.
Monika S KowalczykBroad Institute of Harvard University and MIT, Cambridge, MA 02142, USA.
Carl G de BoerBroad Institute of Harvard University and MIT, Cambridge, MA 02142, USA.
Rebekka K SchneiderDepartment of Medicine, Division of Hematology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Peter G MillerDepartment of Medicine, Division of Hematology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
Marie McConkeyDepartment of Medicine, Division of Hematology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Zuzana TothovaDepartment of Medicine, Division of Hematology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of Harvard University and MIT, Cambridge, MA 02142, USA; Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
Héctor TejeroTranslational Bioinformatics Unit, Spanish National Cancer Research Centre (CNIO), Madrid 28029, Spain.
Dirk HecklDepartment of Medicine, Division of Hematology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Department of Pediatric Hematology and Oncology, Hanover Medical School, Hanover 30625, Germany.
Marcus JäråsDepartment of Medicine, Division of Hematology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Department of Clinical Genetics, Lund University, Lund 22184, Sweden.
Michelle C ChenDepartment of Medicine, Division of Hematology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Hubo LiProgram in Biological and Biomedical Sciences, Harvard Medical School, Boston, MA 02115, USA; Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
Alfred TamayoDepartment of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
Glenn S CowleyBroad Institute of Harvard University and MIT, Cambridge, MA 02142, USA.
Orit Rozenblatt-RosenBroad Institute of Harvard University and MIT, Cambridge, MA 02142, USA.
Fatima Al-ShahrourDepartment of Medicine, Division of Hematology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Translational Bioinformatics Unit, Spanish National Cancer Research Centre (CNIO), Madrid 28029, Spain.
Aviv RegevBroad Institute of Harvard University and MIT, Cambridge, MA 02142, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
Benjamin L EbertDepartment of Medicine, Division of Hematology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of Harvard University and MIT, Cambridge, MA 02142, USA; Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA. Electronic address: bebert@partners.org.
Harvard University · USBrigham and Women's Hospital · USBroad Institute · USDana-Farber Cancer Institute · USHoward Hughes Medical Institute · USLund University · SESpanish National Cancer Research Centre · ES

Funding

VIRUS PRODUCTION COREP30CA014051 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI MATTHEW G. VANDER HEIDEN · 1985 to 2026
$93.9M
TYROSINE KINASE ONCOGENESIS IN MYELOID LEUKEMIAP01CA066996 · NCI · DANA-FARBER CANCER INSTITUTE · PI SCOTT A ARMSTRONG · 1996 to 2026
$52.5M
Medical Scientist Training ProgramT32GM007753 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI WALENSKY, LOREN DAVID · 1985 to 2021
$50.0M
TRAINING IN SLEEP, CIRCADIAN &RESPIRATORY NEUROBIOLOGYT32HL007901 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI Charles A Czeisler · 1998 to 2026
$18.5M
Dana Farber/Harvard Cancer Consortium Career Development Program in Clinical OncologyK12CA087723 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI David Tsai Ting · 2002 to 2026
$17.9M
Functional Genomic Dissection of Refractory AnemiaR01HL082945 · NHLBI · DANA-FARBER CANCER INSTITUTE · PI EBERT, BENJAMIN LEVINE · 2005 to 2022
$6.8M
Howard Hughes Medical InstituteNCI NIH HHS K12 CA087723NCI NIH HHS P01 CA066996NCI NIH HHS P30 CA014051NCI NIH HHS P30-CA14051NHLBI NIH HHS R01 HL082945NHLBI NIH HHS T32 HL007901NIGMS NIH HHS T32 GM007753NIGMS NIH HHS T32GM007753
6 · The paper itself

Abstract

Leukemia stem cells (LSCs) have the capacity to self-renew and propagate disease upon serial transplantation in animal models, and elimination of this cell population is required for curative therapies. Here, we describe a series of pooled, in vivo RNAi screens to identify essential transcription factors (TFs) in a murine model of acute myeloid leukemia (AML) with genetically and phenotypically defined LSCs. These screens reveal the heterodimeric, circadian rhythm TFs Clock and Bmal1 as genes required for the growth of AML cells in vitro and in vivo. Disruption of canonical circadian pathway components produces anti-leukemic effects, including impaired proliferation, enhanced myeloid differentiation, and depletion of LSCs. We find that both normal and malignant hematopoietic cells harbor an intact clock with robust circadian oscillations, and genetic knockout models reveal a leukemia-specific dependence on the pathway. Our findings establish a role for the core circadian clock genes in AML.

Indexed as

AnimalsARNTL Transcription FactorsCircadian RhythmCLOCK ProteinsDisease Models, AnimalGene Knockout TechniquesHematopoiesisHumansLeukemia, Myeloid, AcuteMiceMice, Inbred C57BLNeoplastic Stem CellsRNA InterferenceRNA, Small InterferingARNTL Transcription FactorsBMAL1 protein, humanBmal1 protein, mouseCLOCK protein, humanCLOCK ProteinsRNA, Small Interfering

Identifiers

PMID27058663
PMCPMC4826477
OpenAlexW2326008849

What OpenQuestion holds

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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.