ArticleBlood2010
A germline gain-of-function mutation in Ptpn11 (Shp-2) phosphatase induces myeloproliferative disease by aberrant activation of hematopoietic stem cells.
Article in Blood, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 66 citations in OpenAlex.
- Prognostic significance of SHP2 (PTPN11) expression in solid tumors: A meta-analysis.PloS one · 2022Pooled it
- SFX-01 is therapeutic against myeloproliferative disorders caused by activating mutations in Shp2.EMBO molecular medicine · 2025Article
- Development and validation of machine learning models for the prediction of SH-2 containing protein tyrosine phosphatase 2 inhibitors.Molecular diversity · 2024Article
- Complex Roles ofAnnual review of cancer biology · 2024Article
- Clinical significance of CD166 and HER-2 in different types of gastric cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024Article
- A pan-cancer analysis confirms PTPN11's potential as a prognostic and immunological biomarker.Aging · 2022Article
- Article
- Targeting SHP2 phosphatase in hematological malignancies.Expert opinion on therapeutic targets · 2022Review
- Modeling (not so) rare developmental disorders associated with mutations in the protein-tyrosine phosphatase SHP2.Frontiers in cell and developmental biology · 2022Review
- T cell-specific constitutive active SHP2 enhances T cell memory formation and reduces T cell activation.Frontiers in immunology · 2022Article
- Arsenic exposure increases susceptibility toAmerican journal of translational research · 2022Article
- Review
- Pediatric Neoplasms Presenting with Monocytosis.Current hematologic malignancy reports · 2021Review
- Activating Mutation of SHP2 Establishes a Tumorigenic Phonotype Through Cell-Autonomous and Non-Cell-Autonomous Mechanisms.Frontiers in cell and developmental biology · 2021Review
- Recent advances in genetic predisposition to pediatric acute lymphoblastic leukemia.Expert review of hematology · 2020Review
- PTPσ inhibitors promote hematopoietic stem cell regeneration.Nature communications · 2019Article
- Gain-of-function mutations of Ptpn11 (Shp2) cause aberrant mitosis and increase susceptibility to DNA damage-induced malignancies.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Functions of Shp2 in cancer.Journal of cellular and molecular medicine · 2015Review
- RASopathies: unraveling mechanisms with animal models.Disease models & mechanisms · 2015Review
- Peripheral blood cells from children with RASopathies show enhanced spontaneous colonies growth in vitro and hyperactive RAS signaling.Blood cancer journal · 2015Article
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 4 institutions in 3 countries.
Funding
Abstract
Germline and somatic gain-of-function mutations in tyrosine phosphatase PTPN11 (SHP-2) are associated with juvenile myelomonocytic leukemia (JMML), a myeloproliferative disease (MPD) of early childhood. The mechanism by which PTPN11 mutations induce this disease is not fully understood. Signaling partners that mediate the pathogenic effects of PTPN11 mutations have not been explored. Here we report that germ line mutation Ptpn11(D61G) in mice aberrantly accelerates hematopoietic stem cell (HSC) cycling, increases the stem cell pool, and elevates short-term and long-term repopulating capabilities, leading to the development of MPD. MPD is reproduced in primary and secondary recipient mice transplanted with Ptpn11(D61G/+) whole bone marrow cells or purified Lineage(-)Sca-1(+)c-Kit(+) cells, but not lineage committed progenitors. The deleterious effects of Ptpn11(D61G) mutation on HSCs are attributable to enhancing cytokine/growth factor signaling. The aberrant HSC activities caused by Ptpn11(D61G) mutation are largely corrected by deletion of Gab2, a prominent interacting protein and target of Shp-2 in cell signaling. As a result, MPD phenotypes are markedly ameliorated in Ptpn11(D61G/+)/Gab2(-/-) double mutant mice. Collectively, our data suggest that oncogenic Ptpn11 induces MPD by aberrant activation of HSCs. This study also identifies Gab2 as an important mediator for the pathogenic effects of Ptpn11 mutations.
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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.