ArticleBlood2009
Incomplete restoration of Mpl expression in the mpl-/- mouse produces partial correction of the stem cell-repopulating defect and paradoxical thrombocytosis.
Article in Blood, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 53 citations in OpenAlex.
- Altered thrombopoiesis in spontaneously hypertensive rats.Scientific reports · 2025Article
- Thrombocytopenia in murine schistosomiasis is associated with platelet uptake by liver macrophages that have a distinct activation phenotype.PLoS pathogens · 2025Article
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- Pediatric Bone Marrow Failure: A Broad Landscape in Need of Personalized Management.Journal of clinical medicine · 2023Review
- Molecular Pathogenesis of Myeloproliferative Neoplasms: From Molecular Landscape to Therapeutic Implications.International journal of molecular sciences · 2022Review
- In and out: Traffic and dynamics of thrombopoietin receptor.Journal of cellular and molecular medicine · 2021Review
- The Role of Megakaryocytes in Myelofibrosis.Hematology/oncology clinics of North America · 2021Review
- The Thrombopoietin Receptor, MPL, Is a Therapeutic Target of Opportunity in the MPN.Frontiers in oncology · 2021Review
- Review
- Thrombopoietin is required for full phenotype expression in a JAK2V617F transgenic mouse model of polycythemia vera.PloS one · 2020Article
- Evaluating the Role of Janus Kinase Pathways in Platelet Homeostasis Using a Systems Modeling Approach.CPT: pharmacometrics & systems pharmacology · 2019Article
- Establishment of a congenital amegakaryocytic thrombocytopenia model and a thrombocyte-specific reporter line in zebrafish.Leukemia · 2017Article
- Genetic Alterations of the Thrombopoietin/MPL/JAK2 Axis Impacting Megakaryopoiesis.Frontiers in endocrinology · 2017Review
- The Thrombopoietin Receptor: Structural Basis of Traffic and Activation by Ligand, Mutations, Agonists, and Mutated Calreticulin.Frontiers in endocrinology · 2017Review
- Identification ofFrontiers in endocrinology · 2017Article
- Article
- Article
- Dynamin 2-dependent endocytosis is required for normal megakaryocyte development in mice.Blood · 2015Article
- Article
- Genetic studies reveal an unexpected negative regulatory role for Jak2 in thrombopoiesis.Blood · 2014Article
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5 authors at 1 institution in 1 country.
Funding
Abstract
Expression of Mpl is restricted to hematopoietic cells in the megakaryocyte lineage and to undifferentiated progenitors, where it initiates critical cell survival and proliferation signals after stimulation by its ligand, thrombopoietin (TPO). As a result, a deficiency in Mpl function in patients with congenital amegakaryocytic thrombocytopenia (CAMT) and in mpl(-/-) mice produces profound thrombocytopenia and a severe stem cell-repopulating defect. Gene therapy has the potential to correct the hematopoietic defects of CAMT by ectopic gene expression that restores normal Mpl receptor activity. We rescued the mpl(-/-) mouse with a transgenic vector expressing mpl from the promoter elements of the 2-kb region of DNA just proximal to the natural gene start site. Transgene rescued mice exhibit thrombocytosis but only partial correction of the stem cell defect. Furthermore, they show very low-level expression of Mpl on platelets and megakaryocytes, and the transgene-rescued megakaryocytes exhibit diminished TPO-dependent kinase phosphorylation and reduced platelet production in bone marrow chimeras. Thrombocytosis is an unexpected consequence of reduced Mpl expression and activity. However, impaired TPO homeostasis in the transgene-rescued mice produces elevated plasma TPO levels, which serves as an unchecked stimulus to drive the observed excessive megakaryocytopoiesis.
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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.