ArticleCell reports2015
Myeloid Dysregulation in a Human Induced Pluripotent Stem Cell Model of PTPN11-Associated Juvenile Myelomonocytic Leukemia.
Article in Cell reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 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
51 citing papers in PubMed, 77 citations in OpenAlex.
- MicroRNA Signatures: Illuminating Minimal Residual Disease Monitoring in Juvenile Myelomonocytic Leukemia - A Review.Journal of hematology · 2025Review
- Decoding cancer etiology with cellular reprogramming.Current opinion in genetics & development · 2025Review
- Progression and perspectives in disease modeling for Juvenile myelomonocytic leukemia.Medical oncology (Northwood, London, England) · 2024Review
- Biomarker Landscape in RASopathies.International journal of molecular sciences · 2024Review
- Review
- Discovery of the SHP2 allosteric inhibitor 2-((3R,4R)-4-amino-3-methyl-2-oxa-8-azaspiro[4.5]decan-8-yl)-5-(2,3-dichlorophenyl)-3-methylpyrrolo[2,1-f][1,2,4] triazin-4(3H)-one.Journal of enzyme inhibition and medicinal chemistry · 2023Article
- The role of GATA2 in adult hematopoiesis and cell fate determination.Frontiers in cell and developmental biology · 2023Review
- Merits and challenges of iPSC-derived organoids for clinical applications.Frontiers in cell and developmental biology · 2023Review
- Using Pluripotent Stem Cells to Understand Normal and Leukemic Hematopoietic Development.Stem cells translational medicine · 2022Review
- Developing Bottom-Up Induced Pluripotent Stem Cell Derived Solid Tumor Models Using Precision Genome Editing Technologies.The CRISPR journal · 2022Review
- The seventh international RASopathies symposium: Pathways to a cure-expanding knowledge, enhancing research, and therapeutic discovery.American journal of medical genetics. Part A · 2022Article
- Article
- Increasing Complexity of Molecular Landscapes in Human Hematopoietic Stem and Progenitor Cells during Development and Aging.International journal of molecular sciences · 2022Review
- Review
- Review
- Modeling (not so) rare developmental disorders associated with mutations in the protein-tyrosine phosphatase SHP2.Frontiers in cell and developmental biology · 2022Review
- Patient-derived iPSCs link elevated mitochondrial respiratory complex I function to osteosarcoma in Rothmund-Thomson syndrome.PLoS genetics · 2021Article
- Adenine base editor engineering reduces editing of bystander cytosines.Nature biotechnology · 2021Article
- Review
- Review
Corrections and comments
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Authors and funding
28 authors at 11 institutions in 5 countries.
Funding
Abstract
Somatic PTPN11 mutations cause juvenile myelomonocytic leukemia (JMML). Germline PTPN11 defects cause Noonan syndrome (NS), and specific inherited mutations cause NS/JMML. Here, we report that hematopoietic cells differentiated from human induced pluripotent stem cells (hiPSCs) harboring NS/JMML-causing PTPN11 mutations recapitulated JMML features. hiPSC-derived NS/JMML myeloid cells exhibited increased signaling through STAT5 and upregulation of miR-223 and miR-15a. Similarly, miR-223 and miR-15a were upregulated in 11/19 JMML bone marrow mononuclear cells harboring PTPN11 mutations, but not those without PTPN11 defects. Reducing miR-223's function in NS/JMML hiPSCs normalized myelogenesis. MicroRNA target gene expression levels were reduced in hiPSC-derived myeloid cells as well as in JMML cells with PTPN11 mutations. Thus, studying an inherited human cancer syndrome with hiPSCs illuminated early oncogenesis prior to the accumulation of secondary genomic alterations, enabling us to discover microRNA dysregulation, establishing a genotype-phenotype association for JMML and providing therapeutic targets.
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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.