ArticlePLoS genetics2013
Cooperation between RUNX1-ETO9a and novel transcriptional partner KLF6 in upregulation of Alox5 in acute myeloid leukemia.
Article in PLoS genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 27 citations in OpenAlex.
- CML With Mutant ASXL1 Showed Decreased Sensitivity to TKI Treatment via Upregulation of the ALOX5-BLTR Signaling Pathway.Cancer science · 2025Article
- The role of human 5-Lipoxygenase (5-LO) in carcinogenesis - a question of canonical and non-canonical functions.Oncogene · 2024Review
- Article
- Krüppel-like Factor 6 Suppresses the Progression of Pancreatic Cancer by Upregulating Activating Transcription Factor 3.Journal of clinical medicine · 2022Article
- KDM4B promotes acute myeloid leukemia associated with AML1-ETO by regulating chromatin accessibility.FASEB bioAdvances · 2021Article
- Predictive value of transcriptional expression of Krüppel-like factor-6 (KLF6) in head and neck carcinoma patients treated with radiotherapy.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2021Article
- MicroRNA let-7b downregulates AML1-ETO oncogene expression in t(8;21) AML by targeting its 3'UTR.Experimental hematology & oncology · 2021Article
- Modulation of microRNA processing by 5-lipoxygenase.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Review
- The RUNX1-ETO target gene RASSF2 suppresses t(8;21) AML development and regulates Rac GTPase signaling.Blood cancer journal · 2020Article
- Analysis of Candidate Idarubicin Drug Resistance Genes in MOLT-3 Cells Using Exome Nuclear DNA.Genes · 2018Article
- Article
- Article
- ALOX5 exhibits anti-tumor and drug-sensitizing effects in MLL-rearranged leukemia.Scientific reports · 2017Article
- Survival regulation of leukemia stem cells.Cellular and molecular life sciences : CMLS · 2016Review
- Hmga2 is a direct target gene of RUNX1 and regulates expansion of myeloid progenitors in mice.Blood · 2014Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Fusion protein RUNX1-ETO (AML1-ETO, RUNX1-RUNX1T1) is expressed as the result of the 8q22;21q22 translocation [t(8;21)], which is one of the most common chromosomal abnormalities found in acute myeloid leukemia. RUNX1-ETO is thought to promote leukemia development through the aberrant regulation of RUNX1 (AML1) target genes. Repression of these genes occurs via the recruitment of the corepressors N-COR and SMRT due to their interaction with ETO. Mechanisms of RUNX1-ETO target gene upregulation remain less well understood. Here we show that RUNX1-ETO9a, the leukemogenic alternatively spliced transcript expressed from t(8;21), upregulates target gene Alox5, which is a gene critically required for the promotion of chronic myeloid leukemia development by BCR-ABL. Loss of Alox5 expression reduces activity of RUNX1-ETO9a, MLL-AF9 and PML-RARα in vitro. However, Alox5 is not essential for the induction of leukemia by RUNX1-ETO9a in vivo. Finally, we demonstrate that the upregulation of Alox5 by RUNX1-ETO9a occurs via the C₂H₂ zinc finger transcription factor KLF6, a protein required for early hematopoiesis and yolk sac development. Furthermore, KLF6 is specifically upregulated by RUNX1-ETO in human leukemia cells. This identifies KLF6 as a novel mediator of t(8;21) target gene regulation, providing a new mechanism for RUNX1-ETO transcriptional control.
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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.