Core circadian clock genes regulate leukemia stem cells in AML
Open accessAbstract
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.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Loss of Bmal1 and Clock suppressed leukemogenesis in a prior study, suggesting that circadian disruption can have context-specific effects in different cancers.
“Ebert et al. recently demonstrated that loss of Bmal1 and Clock suppressed leukemogenesis, suggesting that circadian disruption can have context specific effects in different types of cancers (Puram et al., 2016).”
From Circadian Rhythm Disruption Promotes Lung Tumorigenesis (2016) · cites this paper as Puram et al., 2016
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 80 · Cited by 274
- Authors
- Puram, R. V., Kowalczyk, M. S., de Boer, C. G., Schneider, R. K., Miller, P. G., McConkey, M., Tothova, Z., Tejero, H., Heckl, D., Järås, M., Chen, M. C., Li, H., Tamayo, A., Cowley, G. S., Rozenblatt-Rosen, O., Al-Shahrour, F., Regev, A., & Ebert, B. L.
- Affiliations
- Broad Institute (US)
- Brigham and Women's Hospital (US)
- Spanish National Cancer Research Centre (ES)
- Harvard University (US)
- Corresponding author
- Ebert, Benjamin L.
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2016-04
- Volume
- 165
- Issue
- 2
- Pages
- 303-316
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC4826477
- OpenAlex
- W2326008849
- Cited by
- 274
- References
- 80
- Citations by year
- 2026: 20 · 2025: 23 · 2024: 33 · 2023: 32 · 2022: 25 · 2021: 26 · 2020: 28 · 2019: 27 · 2018: 27 · 2017: 18 · 2016: 13 · 2015: 1
- FWCI
- 18.02
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 371 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-sa)
- Lund University Publications (Lund University) (submittedVersion)
- PMC
- Funders
- Howard Hughes Medical Institute
- National Heart, Lung, and Blood Institute (R01HL082945, T32HL007901)
- National Cancer Institute (P01CA066996, P30CA014051, K12CA087723, P30-CA-14051)
- National Institute of General Medical Sciences (T32GM007753)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Keywords
- clock genes, leukemia stem cells, acute myeloid leukemia, clocks, Bmal1, transcription factors, RNAi screen, circadian rhythm, myeloid differentiation
- MeSH terms
- Animals, Circadian Rhythm, Disease Models, Animal, Hematopoiesis, Humans, Mice, Inbred C57BL, Neoplastic Stem Cells, Leukemia, Myeloid, Acute, RNA Interference, RNA, Small Interfering, Mice, Gene Knockout Techniques, CLOCK Proteins, ARNTL Transcription Factors
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
