ArticleBlood2009
Leukemogenic Ptpn11 causes fatal myeloproliferative disorder via cell-autonomous effects on multiple stages of hematopoiesis.
Article in Blood, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers, 1 of them a synthesis that pooled it.
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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
85 citing papers in PubMed, 1 synthesis or guideline pooled it, 120 citations in OpenAlex.
- Molecular Pathogenesis of Chronic Myelomonocytic Leukemia and Potential Molecular Targets for Treatment Approaches.Frontiers in oncology · 2021Pooled it
- Efficacy of the Allosteric MEK Inhibitor Trametinib in Relapsed and Refractory Juvenile Myelomonocytic Leukemia: a Report from the Children's Oncology Group.Cancer discovery · 2024Trial
- Somatic variants activating the RAS-MAPK pathway confer susceptibility to hippocampal sclerosis in drug-resistant epilepsy.bioRxiv : the preprint server for biology · 2026Article
- Innate immune mechanisms hijacked by leukemia-initiating stem cells for selective advantage and immune evasion in Ptpn11-associated JMML.Cell reports · 2025Article
- SFX-01 is therapeutic against myeloproliferative disorders caused by activating mutations in Shp2.EMBO molecular medicine · 2025Article
- Therapeutic Challenges and Emerging Strategies forLife (Basel, Switzerland) · 2025Article
- Oncogenic and microenvironmental signals drive cell type specific apoptosis resistance in juvenile myelomonocytic leukemia.Cell death & disease · 2025Article
- Progression and perspectives in disease modeling for Juvenile myelomonocytic leukemia.Medical oncology (Northwood, London, England) · 2024Review
- Rasopathy-Associated Mutation Ptpn11Cellular and molecular neurobiology · 2024Article
- Allosterically activating SHP2 by oleanolic acid inhibits STAT3-Th17 axis for ameliorating colitis.Acta pharmaceutica Sinica. B · 2024Article
- Developmental effect of RASopathy mutations on neuronal network activity on a chip.Frontiers in cellular neuroscience · 2024Article
- SHP2: A Pleiotropic Target at the Interface of Cancer and Its Microenvironment.Cancer discovery · 2023Review
- Article
- Intramolecular Interaction with the E6 Region Stabilizes the Closed Conformation of the N-SH2 Domain and Concurs with the Self-Inhibitory Docking in Downregulating the Activity of the SHP2 Tyrosine Phosphatase: A Molecular Dynamics Study.International journal of molecular sciences · 2022Article
- Targeting SHP2 phosphatase in hematological malignancies.Expert opinion on therapeutic targets · 2022Review
- Recent advances in the discovery of protein tyrosine phosphatase SHP2 inhibitors.RSC medicinal chemistry · 2022Review
- T cell-specific constitutive active SHP2 enhances T cell memory formation and reduces T cell activation.Frontiers in immunology · 2022Article
- Modeling (not so) rare developmental disorders associated with mutations in the protein-tyrosine phosphatase SHP2.Frontiers in cell and developmental biology · 2022Review
- Review
- Nf1 and Sh2b3 mutations cooperate in vivo in a mouse model of juvenile myelomonocytic leukemia.Blood advances · 2021Article
25 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
7 authors at 4 institutions in 3 countries.
Funding
Abstract
PTPN11, which encodes the tyrosine phosphatase SHP2, is mutated in approximately 35% of patients with juvenile myelomonocytic leukemia (JMML) and at a lower incidence in other neoplasms. To model JMML pathogenesis, we generated knockin mice that conditionally express the leukemia-associated mutant Ptpn11(D61Y). Expression of Ptpn11(D61Y) in all hematopoietic cells evokes a fatal myeloproliferative disorder (MPD), featuring leukocytosis, anemia, hepatosplenomegaly, and factor-independent colony formation by bone marrow (BM) and spleen cells. The Lin(-)Sca1(+)cKit(+) (LSK) compartment is expanded and "right-shifted," accompanied by increased stem cell factor (SCF)-evoked colony formation and Erk and Akt activation. However, repopulating activity is decreased in diseased mice, and mice that do engraft with Ptpn11(D61Y) stem cells fail to develop MPD. Ptpn11(D61Y) common myeloid progenitors (CMPs) and granulocyte-monocyte progenitors (GMPs) produce cytokine-independent colonies in a cell-autonomous manner and demonstrate elevated Erk and Stat5 activation in response to granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulation. Ptpn11(D61Y) megakaryocyte-erythrocyte progenitors (MEPs) yield increased numbers of erythrocyte burst-forming units (BFU-Es), but MEPs and erythrocyte-committed progenitors (EPs) produce fewer erythrocyte colony-forming units (CFU-Es), indicating defective erythroid differentiation. Our studies provide a mouse model for Ptpn11-evoked MPD and show that this disease results from cell-autonomous and distinct lineage-specific effects of mutant Ptpn11 on multiple stages of hematopoiesis.
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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.