ArticleLeukemia2012
Integrated genomic analyses identify WEE1 as a critical mediator of cell fate and a novel therapeutic target in acute myeloid leukemia.
Article in Leukemia, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 2 of them syntheses that pooled 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.
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.
Who cites it
56 citing papers in PubMed, 2 syntheses or guidelines pooled it, 93 citations in OpenAlex.
- A Systematic Review of Candidate miRNAs, Its Targeted Genes and Pathways in Chronic Myeloid Leukemia-An Integrated Bioinformatical Analysis.Frontiers in oncology · 2022Pooled it
- HSC commitment-associated epigenetic signature is prognostic in acute myeloid leukemia.The Journal of clinical investigation · 2014Pooled it
- MAPK signaling cascades mediate distinct glucocorticoid resistance mechanisms in pediatric leukemia.Blood · 2015Trial
- Therapeutic potential of targeting the FLNA-regulated Wee1 kinase in adrenocortical carcinomas.International journal of cancer · 2025Article
- Article
- Synergistic effect of adavosertib and fimepinostat on acute myeloid leukemia cells by enhancing the induction of DNA damage.Investigational new drugs · 2024Article
- Targeting WEE1 kinase as a p53-independent therapeutic strategy in high-risk and relapsed acute lymphoblastic leukemia.Cancer cell international · 2023Article
- Cyclers' kinases in cell division: from molecules to cancer therapy.Cell death and differentiation · 2023Review
- WEE1 and PARP-1 play critical roles in myelodysplastic syndrome and acute myeloid leukemia treatment.Cancer cell international · 2023Article
- Phase 1 study of belinostat and adavosertib in patients with relapsed or refractory myeloid malignancies.Cancer chemotherapy and pharmacology · 2023Article
- Wee1 promotes cell proliferation and imatinib resistance in chronic myeloid leukemia via regulating DNA damage repair dependent on ATM-γH2AX-MDC1.Cell communication and signaling : CCS · 2022Article
- Article
- Targeting the DNA Damage Response for Cancer Therapy by Inhibiting the Kinase Wee1.Frontiers in oncology · 2022Review
- Integrated RNAi screening identifies the NEDDylation pathway as a synergistic partner of azacytidine in acute myeloid leukemia.Scientific reports · 2021Article
- Wee1 Kinase: A Potential Target to Overcome Tumor Resistance to Therapy.International journal of molecular sciences · 2021Review
- SMYD3: a regulator of epigenetic and signaling pathways in cancer.Clinical epigenetics · 2021Review
- Targeting Non-Oncogene Addiction for Cancer Therapy.Biomolecules · 2021Review
- Synthetic Lethality through the Lens of Medicinal Chemistry.Journal of medicinal chemistry · 2020Review
- A WEE1 family business: regulation of mitosis, cancer progression, and therapeutic target.Journal of hematology & oncology · 2020Review
- Therapeutic Target Discovery Using High-Throughput Genetic Screens in Acute Myeloid Leukemia.Cells · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Acute myeloid leukemia (AML) remains a therapeutic challenge despite increasing knowledge about the molecular origins of the disease, as the mechanisms of AML cell escape from chemotherapy remain poorly defined. We hypothesized that AML cells are addicted to molecular pathways in the context of chemotherapy and used complementary approaches to identify these addictions. Using novel molecular and computational approaches, we performed genome-wide short-hairpin RNA screens to identify proteins that mediate AML cell fate after cytarabine exposure; gene expression profiling of AML cells exposed to cytarabine to identify genes with induced expression in this context; and examination of existing gene expression data from primary patient samples. Integration of these independent analyses strongly implicates cell-cycle checkpoint proteins, particularly WEE1, as critical mediators of AML cell survival after cytarabine exposure. Knockdown of WEE1 in a secondary screen confirmed its role in AML cell survival. Pharmacologic inhibition of WEE1 in AML cell lines and primary cells is synergistic with cytarabine. Further experiments demonstrate that inhibition of WEE1 prevents S-phase arrest induced by cytarabine, broadening the functions of WEE1 that may be exploited therapeutically. These data highlight the power of integrating functional and descriptive genomics, and identify WEE1 as a potential therapeutic target in AML.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.