ArticleHaematologica2012
Genetic disruption of the PI3K regulatory subunits, p85α, p55α, and p50α, normalizes mutant PTPN11-induced hypersensitivity to GM-CSF.
Article in Haematologica, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
What it found
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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.
The trial behind it
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
10 citing papers in PubMed, 18 citations in OpenAlex.
- Potential targets of baicalein in macrophages revealed by bulk and single cell RNA sequencing analysis.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- A Comprehensive Review of AIM2 in Cancer: Functional Roles, Molecular Pathways, and Clinical Relevance.Journal of immunology research · 2026Review
- SHP2: A Pleiotropic Target at the Interface of Cancer and Its Microenvironment.Cancer discovery · 2023Review
- Interleukin-15 response signature predicts RhCMV/SIV vaccine efficacy.PLoS pathogens · 2021Article
- SHP-2 in Lymphocytes' Cytokine and Inhibitory Receptor Signaling.Frontiers in immunology · 2019Review
- Role of SHP2 in hematopoiesis and leukemogenesis.Current opinion in hematology · 2017Review
- Germline PTPN11 and somatic PIK3CA variant in a boy with megalencephaly-capillary malformation syndrome (MCAP)--pure coincidence?European journal of human genetics : EJHG · 2015Article
- Protein-tyrosine phosphatase Shp2 positively regulates macrophage oxidative burst.The Journal of biological chemistry · 2015Article
- Molecular profiling of childhood cancer: Biomarkers and novel therapies.BBA clinical · 2014Review
- PI3K p110δ uniquely promotes gain-of-function Shp2-induced GM-CSF hypersensitivity in a model of JMML.Blood · 2014Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Juvenile myelomonocytic leukemia is a lethal disease of children characterized by hypersensitivity of hematopoietic progenitors to granulocyte macrophage-colony stimulating factor. Mutations in PTPN11, the gene encoding the protein tyrosine phosphatase Shp2, are common in juvenile myelomonocytic leukemia and induce hyperactivation of the phosphoinositide-3-kinase pathway. We found that genetic disruption of Pik3r1, the gene encoding the Class IA phosphoinositide-3-kinase regulatory subunits p85α, p55α and p50α, significantly reduced hyperproliferation and hyperphosphorylation of Akt in gain-of-function Shp2 E76K-expressing cells. Elevated protein levels of the phosphoinositide-3-kinase catalytic subunit, p110δ, in the Shp2 E76K-expressing Pik3r1-/- cells suggest that p110δ may be a crucial mediator of mutant Shp2-induced phosphoinositide-3-kinase hyperactivation. Consistently, treatment with the p110δ-specific inhibitor, IC87114, or the clinical grade pan-phosphoinositide-3-kinase inhibitor, GDC-0941, reduced granulocyte macrophage-colony stimulating factor hypersensitivity. Treatment with the farnesyltransferase inhibitor, tipifarnib, showed that Shp2 E76K induces hyperactivation of phosphoinositide-3-kinase by both Ras-dependent and Ras-independent mechanisms. Collectively, these findings implicate Class IA phosphoinositide-3-kinase as a relevant molecular target in juvenile myelomonocytic leukemia.
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Registered trials
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