ArticleGenes & development2010
Developmental stage-specific interplay of GATA1 and IGF signaling in fetal megakaryopoiesis and leukemogenesis.
Article in Genes & development, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.
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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.
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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
81 citing papers in PubMed, 142 citations in OpenAlex.
- The effect of cohesin mutations on HLA-class II expression in the myeloid leukemia of Down syndrome.Leukemia · 2026Article
- Single-cell transcriptomics reveal individual and cooperative effects of trisomy 21 and GATA1s on hematopoiesis.Stem cell reports · 2025Article
- The role of the haematopoietic stem cell niche in development and ageing.Nature reviews. Molecular cell biology · 2025Review
- Malignant progression of preleukemic disorders.Blood · 2024Review
- Quantitative label-free mass spectrometry reveals content and signaling differences between neonatal and adult platelets.Journal of thrombosis and haemostasis : JTH · 2024Article
- Interplay of IGF1R and estrogen signaling regulates hematopoietic stem and progenitor cells.bioRxiv : the preprint server for biology · 2024Article
- Down syndrome-associated leukaemias: current evidence and challenges.Therapeutic advances in hematology · 2024Review
- Synergistic roles of DYRK1A and GATA1 in trisomy 21 megakaryopoiesis.JCI insight · 2023Article
- RUN(X) out of blood: emerging RUNX1 functions beyond hematopoiesis and links to Down syndrome.Human genomics · 2023Review
- Layered immunity and layered leukemogenicity: Developmentally restricted mechanisms of pediatric leukemia initiation.Immunological reviews · 2023Review
- RUNX1 isoform disequilibrium promotes the development of trisomy 21-associated myeloid leukemia.Blood · 2023Article
- Distinct niche structures and intrinsic programs of fallopian tube and ovarian surface epithelial cells.iScience · 2023Article
- Mechanism of KIT gene regulation by GATA1 lacking the N-terminal domain in Down syndrome-related myeloid disorders.Scientific reports · 2022Article
- Stepwise GATA1 and SMC3 mutations alter megakaryocyte differentiation in a Down syndrome leukemia model.The Journal of clinical investigation · 2022Article
- Fetal vs adult megakaryopoiesis.Blood · 2022Article
- Article
- Detoxified pneumolysin derivative ΔA146Ply inhibits autophagy and induces apoptosis in acute myeloid leukemia cells by activating mTOR signaling.Experimental & molecular medicine · 2022Article
- Article
- Review
- SON inhibits megakaryocytic differentiation via repressing RUNX1 and the megakaryocytic gene expression program in acute megakaryoblastic leukemia.Cancer gene therapy · 2021Article
21 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Oncogene-mediated transformation of hematopoietic cells has been studied extensively, but little is known about the molecular basis for restriction of oncogenes to certain target cells and differential cellular context-specific requirements for oncogenic transformation between infant and adult leukemias. Understanding cell type-specific interplay of signaling pathways and oncogenes is essential for developing targeted cancer therapies. Here, we address the vexing issue of how developmental restriction is achieved in Down syndrome acute megakaryoblastic leukemia (DS-AMKL), characterized by the triad of fetal origin, mutated GATA1 (GATA1s), and trisomy 21. We demonstrate overactivity of insulin-like growth factor (IGF) signaling in authentic human DS-AMKL and in a DS-AMKL mouse model generated through retroviral insertional mutagenesis. Fetal but not adult megakaryocytic progenitors are dependent on this pathway. GATA1 restricts IGF-mediated activation of the E2F transcription network to coordinate proliferation and differentiation. Failure of a direct GATA1-E2F interaction in mutated GATA1s converges with overactive IGF signaling to promote cellular transformation of DS fetal progenitors, revealing a complex, fetal stage-specific regulatory network. Our study underscores context-dependent requirements during oncogenesis, and explains resistance to transformation of ostensibly similar adult progenitors.
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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.