ArticleProceedings of the National Academy of Sciences of the United States of America2013
TP53 suppression promotes erythropoiesis in del(5q) MDS, suggesting a targeted therapeutic strategy in lenalidomide-resistant patients.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02243124 (A Study of Aezea®), which is not on this map. Cited by 25 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.
A Study of Aezea® (Cenersen) in Transfusion Dependent Anemia Associated With Myelodysplastic Syndrome
Who cites it
25 citing papers in PubMed, 53 citations in OpenAlex.
- The transcriptomic landscape of normal and ineffective erythropoiesis at single-cell resolution.Blood advances · 2023Article
- TP53 in Myelodysplastic Syndromes.Cancers · 2021Review
- Novel Molecular Mechanism of Lenalidomide in Myeloid Malignancies Independent of Deletion of Chromosome 5q.Cancers · 2021Review
- Single-cell analysis of erythropoiesis in Rpl11 haploinsufficient mice reveals insight into the pathogenesis of Diamond-Blackfan anemia.Experimental hematology · 2021Article
- Ribosomopathies: New Therapeutic Perspectives.Cells · 2020Review
- MYSM1 maintains ribosomal protein gene expression in hematopoietic stem cells to prevent hematopoietic dysfunction.JCI insight · 2020Article
- Review
- Protein Carbonylation in Patients with Myelodysplastic Syndrome: An Opportunity for Deferasirox Therapy.Antioxidants (Basel, Switzerland) · 2019Article
- Pan-myeloid Differentiation of Human Cord Blood Derived CD34+ Hematopoietic Stem and Progenitor Cells.Journal of visualized experiments : JoVE · 2019Article
- Single-cell analyses demonstrate that a heme-GATA1 feedback loop regulates red cell differentiation.Blood · 2019Article
- Mechanisms of leukemic transformation in congenital neutropenia.Current opinion in hematology · 2019Review
- Effect ofOncotarget · 2018Article
- Article
- HDAC8 regulates long-term hematopoietic stem-cell maintenance under stress by modulating p53 activity.Blood · 2017Article
- The U2AF1S34F mutation induces lineage-specific splicing alterations in myelodysplastic syndromes.The Journal of clinical investigation · 2017Article
- Cryptic splicing events in the iron transporter ABCB7 and other key target genes in SF3B1-mutant myelodysplastic syndromes.Leukemia · 2016Article
- Identification of microRNA-regulated pathways using an integration of microRNA-mRNA microarray and bioinformatics analysis in CD34+ cells of myelodysplastic syndromes.Scientific reports · 2016Article
- Efficacy and Mechanism of Action of Low Dose Emetine against Human Cytomegalovirus.PLoS pathogens · 2016Article
- Molecular and Cellular Mechanisms of Myelodysplastic Syndrome: Implications on Targeted Therapy.International journal of molecular sciences · 2016Review
- Ribosomopathies: how a common root can cause a tree of pathologies.Disease models & mechanisms · 2015Review
Corrections and comments
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Authors and funding
21 authors at 4 institutions in 4 countries.
Funding
Abstract
Stabilization of p53 in erythroid precursors in response to nucleosomal stress underlies the hypoplastic anemia in myelodysplastic syndromes (MDS) with chromosome 5q deletion [del(5q)]. We investigated whether cenersen, a clinically active 20-mer antisense oligonucleotide complementary to TP53 exon10, could suppress p53 expression and restore erythropoiesis in del(5q) MDS. Cenersen treatment of ribosomal protein S-14-deficient erythroblasts significantly reduced cellular p53 and p53-up-regulated modulator of apoptosis expression compared with controls, accompanied by a significant reduction in apoptosis and increased cell proliferation. In a two-stage erythroid differentiation assay, cenersen significantly suppressed nuclear p53 in bone marrow CD34+ cells isolated from patients with del(5q) MDS, whereas erythroid burst recovery increased proportionally to the magnitude of p53 suppression without evidence of del(5q) clonal suppression (r = -0.6; P = 0.005). To explore the effect of p53 suppression on erythropoiesis in vivo, dexamethasone, a glucocorticoid receptor-dependent p53 antagonist, was added to lenalidomide treatment in eight lower-risk, transfusion-dependent, del(5q) MDS patients with acquired drug resistance. Transfusion independence was restored in five patients accompanied by expansion of erythroid precursors and decreased cellular p53 expression. We conclude that targeted suppression of p53 could support effective erythropoiesis in lenalidomide-resistant del(5q) MDS.
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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.