ArticleJournal of cellular physiology2010
CXCR4-independent rescue of the myeloproliferative defect of the Gata1low myelofibrosis mouse model by Aplidin.
Article in Journal of cellular physiology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 18 citations in OpenAlex.
- Evaluation of plitidepsin in patients with primary myelofibrosis and post polycythemia vera/essential thrombocythemia myelofibrosis: results of preclinical studies and a phase II clinical trial.Blood cancer journal · 2015Trial
- The Variation in the Traits Ameliorated by Inhibitors of JAK1/2, TGF-β, P-Selectin, and CXCR1/CXCR2 in theInternational journal of molecular sciences · 2024Article
- Non-Pharmacologic Management of Splenomegaly for Patients with Myelofibrosis: Is There Any Role for Splenectomy or Splenic Radiation in 2020?Current hematologic malignancy reports · 2020Review
- Modern management of splenomegaly in patients with myelofibrosis.Annals of hematology · 2020Review
- Understanding Splenomegaly in Myelofibrosis: Association with Molecular Pathogenesis.International journal of molecular sciences · 2018Review
- GATA1 insufficiencies in primary myelofibrosis and other hematopoietic disorders: consequences for therapy.Expert review of hematology · 2018Review
- Porphyromonas gingivalis lipopolysaccharide stimulation in human periodontal ligament stem cells: role of epigenetic modifications to the inflammation.European journal of histochemistry : EJH · 2017Article
- Activation of non-canonical TGF-β1 signaling indicates an autoimmune mechanism for bone marrow fibrosis in primary myelofibrosis.Blood cells, molecules & diseases · 2015Article
- Preclinical models for drug selection in myeloproliferative neoplasms.Current hematologic malignancy reports · 2013Review
- Characterization of the TGF-β1 signaling abnormalities in the Gata1low mouse model of myelofibrosis.Blood · 2013Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 3 countries.
Funding
Abstract
The discovery of JAK2 mutations in Philadelphia-negative myeloproliferative neoplasms has prompted investigators to evaluate mutation-targeted treatments to restore hematopoietic cell functions in these diseases. However, the results of the first clinical trials with JAK2 inhibitors are not as promising as expected, prompting a search for additional drugable targets to treat these disorders. In this paper, we used the hypomorphic Gata1(low) mouse model of primary myelofibrosis (PMF), the most severe of these neoplasms, to test the hypothesis that defective marrow hemopoiesis and development of extramedullary hematopoiesis in myelofibrosis is due to insufficient p27(Kip1) activity and is treatable by Aplidin, a cyclic depsipeptide that activates p27(Kip1) in several cancer cells. Aplidin restored expression of Gata1 and p27(Kip1) in Gata1(low) hematopoietic cells, proliferation of marrow progenitor cells in vitro and maturation of megakaryocytes in vivo (reducing TGF-beta/VEGF levels released in the microenvironment by immature Gata1(low) megakaryocytes). Microvessel density, fibrosis, bone growth, and marrow cellularity were normal in Aplidin-treated mice and extramedullary hematopoiesis did not develop in liver although CXCR4 expression in Gata1(low) progenitor cells remained low. These results indicate that Aplidin effectively alters the natural history of myelofibrosis in Gata1(low) mice and suggest this drug as candidate for clinical evaluation in PMF.
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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 Socratic graph.