ArticlePloS one2009
Oncogenic RAS enables DNA damage- and p53-dependent differentiation of acute myeloid leukemia cells in response to chemotherapy.
Article in PloS one, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 31 citations in OpenAlex.
- BAYESIAN EMPIRICAL LIKELIHOOD FOR ULTRA-HIGH DIMENSIONAL VARIABLE SELECTION WITH APPLICATION TO DRUG SENSITIVITY.The annals of applied statistics · 2026Article
- Impact of p53-associated acute myeloid leukemia hallmarks on metabolism and the immune environment.Frontiers in pharmacology · 2024Review
- Validation of the ALFA-1200 model in older patients with AML treated with intensive chemotherapy.Blood advances · 2023Article
- Bone marrow stromal cells reduce low-dose cytarabine-induced differentiation of acute myeloid leukemia.Frontiers in pharmacology · 2023Article
- Integrative analysis identifies an older female-linked AML patient group with better risk in ECOG-ACRIN Cancer Research Group's clinical trial E3999.Blood cancer journal · 2022Article
- Analysis of RAS gene mutations in cytogenetically normal de novo acute myeloid leukemia patients reveals some novel alterations.Saudi journal of biological sciences · 2021Article
- Combinatorial targeting of XPO1 and FLT3 exerts synergistic anti-leukemia effects through induction of differentiation and apoptosis inHaematologica · 2018Article
- Glioblastoma and acute myeloid leukemia: malignancies with striking similarities.Journal of neuro-oncology · 2018Review
- [Immunotherapy of cancer with checkpoint inhibitors : Not only in malignant melanoma].Der Internist · 2017Review
- Hydroxylated Dimeric Naphthoquinones Increase the Generation of Reactive Oxygen Species, Induce Apoptosis of Acute Myeloid Leukemia Cells and Are Not Substrates of the Multidrug Resistance Proteins ABCB1 and ABCG2.Pharmaceuticals (Basel, Switzerland) · 2016Article
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- Modulation of Ras signaling alters the toxicity of hydroquinone, a benzene metabolite and component of cigarette smoke.BMC cancer · 2014Article
- Ras/Raf/MEK/ERK Pathway Activation in Childhood Acute Lymphoblastic Leukemia and Its Therapeutic Targeting.Frontiers in oncology · 2014Review
- A novel application of furazolidone: anti-leukemic activity in acute myeloid leukemia.PloS one · 2013Article
- MYCN transgenic zebrafish model with the characterization of acute myeloid leukemia and altered hematopoiesis.PloS one · 2013Article
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- ATP depletion triggers acute myeloid leukemia differentiation through an ATR/Chk1 protein-dependent and p53 protein-independent pathway.The Journal of biological chemistry · 2012Article
- Flt3-ITD alters chemotherapy response in vitro and in vivo in a p53-dependent manner.Experimental hematology · 2011Article
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Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Acute myeloid leukemia (AML) is a clonal disease originating from myeloid progenitor cells with a heterogeneous genetic background. High-dose cytarabine is used as the standard consolidation chemotherapy. Oncogenic RAS mutations are frequently observed in AML, and are associated with beneficial response to cytarabine. Why AML-patients with oncogenic RAS benefit most from high-dose cytarabine post-remission therapy is not well understood. Here we used bone marrow cells expressing a conditional MLL-ENL-ER oncogene to investigate the interaction of oncogenic RAS and chemotherapeutic agents. We show that oncogenic RAS synergizes with cytotoxic agents such as cytarabine in activation of DNA damage checkpoints, resulting in a p53-dependent genetic program that reduces clonogenicity and increases myeloid differentiation. Our data can explain the beneficial effects observed for AML patients with oncogenic RAS treated with higher dosages of cytarabine and suggest that induction of p53-dependent differentiation, e.g. by interfering with Mdm2-mediated degradation, may be a rational approach to increase cure rate in response to chemotherapy. The data also support the notion that the therapeutic success of cytotoxic drugs may depend on their ability to promote the differentiation of tumor-initiating cells.
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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.