ArticleLeukemia2013
AKT collaborates with ERG and Gata1s to dysregulate megakaryopoiesis and promote AMKL.
Article in Leukemia, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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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.
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Who cites it
19 citing papers in PubMed, 29 citations in OpenAlex.
- Genome-wide association study of somatic GATA1s mutations in newborns with Down syndrome.Blood advances · 2025Article
- c-Mpl-del, a c-Mpl alternative splicing isoform, promotes AMKL progression and chemoresistance.Cell death & disease · 2022Article
- Regulatory T cells promote the stemness of leukemia stem cells through IL10 cytokine-related signaling pathway.Leukemia · 2022Article
- Advances in molecular characterization of myeloid proliferations associated with Down syndrome.Frontiers in genetics · 2022Review
- Article
- Hyper-SUMOylation of ERG Is Essential for the Progression of Acute Myeloid Leukemia.Frontiers in molecular biosciences · 2021Article
- Acute Megakaryocytic Leukemia.Cold Spring Harbor perspectives in medicine · 2020Review
- GATA1 gene silencing inhibits invasion, proliferation and migration of cholangiocarcinoma stem cells via disrupting the PI3K/AKT pathway.OncoTargets and therapy · 2019Article
- Synergistic Activity with NOTCH Inhibition and Androgen Ablation in ERG-Positive Prostate Cancer Cells.Molecular cancer research : MCR · 2017Article
- Down syndrome and the complexity of genome dosage imbalance.Nature reviews. Genetics · 2017Review
- Decitabine-Induced Changes in Human Myelodysplastic Syndrome Cell Line SKM-1 Are Mediated by FOXO3A Activation.Journal of immunology research · 2017Article
- Article
- The emerging role of GATA transcription factors in development and disease.Expert reviews in molecular medicine · 2016Review
- Intragenic ERG Deletions Do Not Explain the Biology of ERG-Related Acute Lymphoblastic Leukemia.PloS one · 2016Article
- Myeloid Proliferations Associated with Down Syndrome.Journal of hematopathology · 2015Article
- The secret life of a megakaryocyte: emerging roles in bone marrow homeostasis control.Cellular and molecular life sciences : CMLS · 2015Review
- Extracellular signal-regulated kinase signaling regulates the opposing roles of JUN family transcription factors at ETS/AP-1 sites and in cell migration.Molecular and cellular biology · 2015Article
- GATA1s induces hyperproliferation of eosinophil precursors in Down syndrome transient leukemia.Leukemia · 2014Article
- AKT is a therapeutic target in myeloproliferative neoplasms.Leukemia · 2013Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The requirement that leukemic Gata1 mutations be present in cells harboring trisomy 21 led to the discovery that overexpression of ERG drives aberrant megakaryopoiesis. Given that constitutive PI3K/AKT signaling is a frequent component of hematologic malignancies and the relationship between AKT and Notch in this lineage, we studied the crosstalk between AKT signaling and ERG in megakaryopoiesis. We discovered that constitutive AKT signaling is associated with a dramatic increase in apoptosis of WT megakaryocytes (MKs), but that overexpression of ERG blocks AKT-induced death. We further found that Gata1 mutations protect MKs from activated AKT-induced apoptosis. As a consequence, however, the enhanced signaling inhibits differentiation of Gata1 mutant, but not WT, MKs. Gata1 mutant cells that overexpress ERG with hyperactive AKT are characterized by diminished FOXO1/3a expression and an increased dependency on the c-Jun pathway similar to that seen in acute megakaryoblastic leukemia (AMKL) cell lines, acute myeloid leukemia (AML) with knockdown of FOXO3a, or AML with expression of myristoylated Akt. Additionally, we found that the AKT allosteric inhibitor MK2206 caused reduced cell viability and proliferation of AMKL cell lines. The contribution of aberrant AKT signaling during the ontogeny of Down syndrome-transient myeloproliferative disorder/AMKL indicates that AKT is a therapeutic target in this form of AML.
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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.