ArticleBlood2009
Identification of AML1-ETO modulators by chemical genomics.
Article in Blood, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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The trial behind it
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Who cites it
25 citing papers in PubMed, 46 citations in OpenAlex.
- Modeling and therapeutic targeting of t(8;21) AML with/without TP53 deficiency.International journal of hematology · 2024Article
- Identification of the global miR-130a targetome reveals a role for TBL1XR1 in hematopoietic stem cell self-renewal and t(8;21) AML.Cell reports · 2022Article
- Defining the transcriptional control of pediatric AML highlights RARA as a superenhancer-regulated druggable dependency.Blood advances · 2021Article
- Irinotecan Induces Disease Remission in Xenograft Mouse Models of PediatricBiomedicines · 2021Article
- Clinical Implications of Inflammation in Acute Myeloid Leukemia.Frontiers in oncology · 2021Review
- An update on the molecular pathogenesis and potential therapeutic targeting of AML with t(8;21)(q22;q22.1);RUNX1-RUNX1T1.Blood advances · 2020Review
- TAF1 plays a critical role in AML1-ETO driven leukemogenesis.Nature communications · 2019Article
- Article
- Therapeutic Targeting of Notch Signaling Pathway in Hematological Malignancies.Mediterranean journal of hematology and infectious diseases · 2019Review
- Glucocorticoids Inhibit Oncogenic RUNX1-ETO in Acute Myeloid Leukemia with Chromosome Translocation t(8;21).Theranostics · 2018Article
- Genome-wide co-occupancy of AML1-ETO and N-CoR defines the t(8;21) AML signature in leukemic cells.BMC genomics · 2015Article
- Comparison of plasmid DNA versus PCR amplified gene of insert DNA for nucleofection in Kasumi-1 cells.Cytotechnology · 2015Article
- Identification of the Adapter Molecule MTSS1 as a Potential Oncogene-Specific Tumor Suppressor in Acute Myeloid Leukemia.PloS one · 2015Article
- Esculetin Downregulates the Expression of AML1-ETO and C-Kit in Kasumi-1 Cell Line by Decreasing Half-Life of mRNA.Journal of oncology · 2015Article
- Gene signature critical to cancer phenotype as a paradigm for anticancer drug discovery.Oncogene · 2013Article
- AML1-ETO targets and suppresses cathepsin G, a serine protease, which is able to degrade AML1-ETO in t(8;21) acute myeloid leukemia.Oncogene · 2013Article
- SIAH proteins: critical roles in leukemogenesis.Leukemia · 2013Review
- Complementary genomic screens identify SERCA as a therapeutic target in NOTCH1 mutated cancer.Cancer cell · 2013Article
- AML1-ETO driven acute leukemia: insights into pathogenesis and potential therapeutic approaches.Frontiers of medicine · 2012Review
- Depletion of RUNX1/ETO in t(8;21) AML cells leads to genome-wide changes in chromatin structure and transcription factor binding.Leukemia · 2012Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Somatic rearrangements of transcription factors are common abnormalities in the acute leukemias. With rare exception, however, the resultant protein products have remained largely intractable as pharmacologic targets. One example is AML1-ETO, the most common translocation reported in acute myeloid leukemia (AML). To identify AML1-ETO modulators, we screened a small molecule library using a chemical genomic approach. Gene expression signatures were used as surrogates for the expression versus loss of the translocation in AML1-ETO-expressing cells. The top classes of compounds that scored in this screen were corticosteroids and dihydrofolate reductase (DHFR) inhibitors. In addition to modulating the AML1-ETO signature, both classes induced evidence of differentiation, dramatically inhibited cell viability, and ultimately induced apoptosis via on-target activity. Furthermore, AML1-ETO-expressing cell lines were exquisitely sensitive to the effects of corticosteroids on cellular viability compared with nonexpressers. The corticosteroids diminished AML1-ETO protein in AML cells in a proteasome- and glucocorticoid receptor-dependent manner. Moreover, these molecule classes demonstrated synergy in combination with standard AML chemotherapy agents and activity in an orthotopic model of AML1-ETO-positive AML. This work suggests a role for DHFR inhibitors and corticosteroids in treating patients with AML1-ETO-positive disease.
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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.