ArticleThe Journal of clinical investigation2011
PML-RARA can increase hematopoietic self-renewal without causing a myeloproliferative disease in mice.
Article in The Journal of clinical investigation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 37 citations in OpenAlex.
- Acute Promyelocytic Leukemia, Retinoic Acid, and Arsenic: A Tale of Dualities.Cold Spring Harbor perspectives in medicine · 2024Review
- Article
- The Impact of the Cellular Origin in Acute Myeloid Leukemia: Learning From Mouse Models.HemaSphere · 2019Review
- Smc3 is required for mouse embryonic and adult hematopoiesis.Experimental hematology · 2019Article
- Dual origin of relapses in retinoic-acid resistant acute promyelocytic leukemia.Nature communications · 2018Article
- HDAC3 activity is required for initiation of leukemogenesis in acute promyelocytic leukemia.Leukemia · 2017Article
- Pathways of retinoid synthesis in mouse macrophages and bone marrow cells.Journal of leukocyte biology · 2016Article
- PML-RARA requires DNA methyltransferase 3A to initiate acute promyelocytic leukemia.The Journal of clinical investigation · 2016Article
- Transcription and methylation analyses of preleukemic promyelocytes indicate a dual role for PML/RARA in leukemia initiation.Haematologica · 2015Article
- Absence of natural intracellular retinoids in mouse bone marrow cells and implications for PML-RARA transformation.Blood cancer journal · 2015Article
- Dynamics of leukemia stem-like cell extinction in acute promyelocytic leukemia.Cancer research · 2014Article
- Article
- PML-mediated signaling and its role in cancer stem cells.Oncogene · 2014Review
- Integrated analysis of miRNA and mRNA during differentiation of human CD34+ cells delineates the regulatory roles of microRNA in hematopoiesis.Experimental hematology · 2014Article
- Review
- Article
- IGF binding protein 2 is a cell-autonomous factor supporting survival and migration of acute leukemia cells.Journal of hematology & oncology · 2013Article
- Notch signaling in acute promyelocytic leukemia.Leukemia · 2013Article
- The Impact of FLT3 Mutations on the Development of Acute Myeloid Leukemias.Leukemia research and treatment · 2013Article
- Dynamic HoxB4-regulatory network during embryonic stem cell differentiation to hematopoietic cells.Blood · 2012Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Acute promyelocytic leukemia (APL) is characterized by the t(15;17) translocation that generates the fusion protein promyelocytic leukemia-retinoic acid receptor α (PML-RARA) in nearly all cases. Multiple prior mouse models of APL constitutively express PML-RARA from a variety of non-Pml loci. Typically, all animals develop a myeloproliferative disease, followed by leukemia in a subset of animals after a long latent period. In contrast, human APL is not associated with an antecedent stage of myeloproliferation. To address this discrepancy, we have generated a system whereby PML-RARA expression is somatically acquired from the mouse Pml locus in the context of Pml haploinsufficiency. We found that physiologic PML-RARA expression was sufficient to direct a hematopoietic progenitor self-renewal program in vitro and in vivo. However, this expansion was not associated with evidence of myeloproliferation, more accurately reflecting the clinical presentation of human APL. Thus, at physiologic doses, PML-RARA primarily acts to increase hematopoietic progenitor self-renewal, expanding a population of cells that are susceptible to acquiring secondary mutations that cause progression to leukemia. This mouse model provides a platform for more accurately dissecting the early events in APL pathogenesis.
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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.