PU.1 is essential for MLL leukemia partially via crosstalk with the MEIS/HOX pathway
Open accessAbstract
Mixed lineage leukemia (MLL) fusion proteins directly activate the expression of key downstream genes such as MEIS1, HOXA9 to drive an aggressive form of human leukemia. However, it is still poorly understood what additional transcriptional regulators, independent of the MLL fusion pathway, contribute to the development of MLL leukemia. Here we show that the transcription factor PU.1 is essential for MLL leukemia and is required for the growth of MLL leukemic cells via the promotion of cell-cycle progression and inhibition of apoptosis. Importantly, PU.1 expression is not under the control of MLL fusion proteins. We further identified a PU.1-governed 15-gene signature, which contains key regulators in the MEIS-HOX program (MEIS1, PBX3, FLT3, and c-KIT). PU.1 directly binds to the genomic loci of its target genes in vivo, and is required to maintain active expression of those genes in both normal hematopoietic stem and progenitor cells and in MLL leukemia. Finally, the clinical significance of the identified PU.1 signature was indicated by its ability to predict survival in acute myelogenous leukemia patients. Together, our findings demonstrate that PU.1 contributes to the development of MLL leukemia, partially via crosstalk with the MEIS/HOX pathway.
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?
Reduced PU.1 expression in haematopoietic cells leads to reduced growth and transformative capability in several leukaemic mouse models including AML.
“Reduced PU.1 expression in haematopoietic cells leads to reduced growth and transformative capability in several leukaemic mouse models including AML.43”
From Vitamin C-induced epigenomic remodelling in IDH1 mutant acute myeloid leukaemia (2018) · cites this paper as [43]
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 58 · Cited by 53
Research works printed but not linked: 1
- [22]Mann RS Lelli KM Joshi R Hox specificity: unique roles for cofactors and collaborators Curr Top Dev Biol 2009 88 63 101 19651302 PMC2810641
- Authors
- Zhou, J., Wu, J., Li, B., Liu, D., Yu, J., Yan, X., Zheng, S., Wang, J., Zhang, L., Zhang, L., He, F., Li, Q., Chen, A., Zhang, Y., Zhao, X., Guan, Y., Zhao, X., Yan, J., Ni, J., Nobrega, M. A., Löwenberg, B., Delwel, R., Valk, P. J. M., Kumar, A., Xie, L., Tenen, D. G., Huang, G., & Wang, Q.-F.
- Affiliations
- Chinese Academy of Sciences (CN)
- Cincinnati Children's Hospital Medical Center (US)
- Shanghai Center For Bioinformation Technology (CN)
- First Hospital of Jilin University (CN)
- Erasmus MC (NL)
- Harvard University (US)
- Corresponding author
- Huang, G
- Wang, Q-f
- ORCID
- Venue
- Leukemia
- Published
- 2013-12-26
- Volume
- 28
- Issue
- 7
- Pages
- 1436-1448
- ISSN
- 0887-6924 (ISSN-L)
- 1476-5551
- PMC
- PMC4410691
- OpenAlex
- W2044048386
- Cited by
- 53
- References
- 58
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 1 · 2023: 3 · 2022: 2 · 2021: 4 · 2020: 4 · 2019: 5 · 2018: 7 · 2017: 7 · 2016: 6 · 2015: 7 · 2014: 1
- FWCI
- 3.35
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Leukemia (publishedVersion)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- PubMed Central (acceptedVersion)
- Rare & Special e-Zone (The Hong Kong University of Science and Technology) (submittedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
- Funders
- National Heart, Lung, and Blood Institute (R01HL112719, R01HL111192)
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK090971)
- Topics
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Acute Lymphoblastic Leukemia research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
- Keywords
- PU.1, MLL leukemia, MEIS1, HOXA9, PBX3, FLT3, CD117, transcriptional regulation, cell cycle progression, apoptosis inhibition, gene expression signatures, hematopoietic stem and progenitor cells, acute myeloid leukemia, survival prediction
- MeSH terms
- Myeloid Ecotropic Viral Integration Site 1 Protein, Proto-Oncogene Protein Spi-1, Animals, Cell Transformation, Neoplastic, Disease Models, Animal, Humans, Neoplasm Proteins, Prognosis, Proto-Oncogene Proteins, Leukemia, Biphenotypic, Acute, Oncogene Proteins, Fusion, Trans-Activators, Gene Expression Regulation, Leukemic, Cluster Analysis, Homeodomain Proteins, Gene Expression Profiling, Cell Line, Tumor, Mice
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
