ArticleProceedings of the National Academy of Sciences of the United States of America2002
PML/RARalpha and FLT3-ITD induce an APL-like disease in a mouse model.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 111 papers.
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Who cites it
111 citing papers in PubMed, 331 citations in OpenAlex.
- Arsenic trioxide in front-line therapy of acute promyelocytic leukemia (C9710): prognostic significance of FLT3 mutations and complex karyotype.Leukemia & lymphoma · 2014Trial
- High-dose cytarabine and mitoxantrone in consolidation therapy for acute promyelocytic leukemia.Leukemia · 2005Trial
- Differentiation therapy in acute myeloid leukaemia: molecular basis, clinical progress, and future perspectives.Frontiers in medicine · 2026Review
- CPSF6-RARγ interacts with histone deacetylase 3 to promote myeloid transformation in RARG-fusion acute myeloid leukemia.Nature communications · 2025Article
- PML::RARA and GATA2 proteins interact via DNA templates to induce aberrant self-renewal in mouse and human hematopoietic cells.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- A machine learning model identifies M3-like subtype in AML based on PML/RARα targets.iScience · 2024Article
- Function of PML-RARA in Acute Promyelocytic Leukemia.Advances in experimental medicine and biology · 2024Review
- Children's Oncology Group's 2023 blueprint for research: Myeloid neoplasms.Pediatric blood & cancer · 2023Article
- Acute promyelocytic leukaemia: population-based study of epidemiology and outcome with ATRA and oral-ATO from 1991 to 2021.BMC cancer · 2023Article
- Targeting Pim kinases in hematological cancers: molecular and clinical review.Molecular cancer · 2023Review
- Article
- Discovery of druggable cancer-specific pathways with application in acute myeloid leukemia.GigaScience · 2022Article
- ASXL1/2 mutations and myeloid malignancies.Journal of hematology & oncology · 2022Review
- A review of FLT3 inhibitors in acute myeloid leukemia.Blood reviews · 2022Review
- Therapeutic Targeting of FLT3 in Acute Myeloid Leukemia: Current Status and Novel Approaches.OncoTargets and therapy · 2022Review
- Activating Mutation in the Receptor Tyrosine Kinase FLT3 with Clinicopathological Relevance in Canine Mast Cell Tumors.Veterinary medicine international · 2022Article
- Discovery of a first-in-class CDK2 selective degrader for AML differentiation therapy.Nature chemical biology · 2021Article
- Descriptive and Functional Genomics in Acute Myeloid Leukemia (AML): Paving the Road for a Cure.Cancers · 2021Review
- Review
- Mouse Models of Myeloid Malignancies.Cold Spring Harbor perspectives in medicine · 2021Review
51 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Acute promyelocytic leukemia (APL) cells invariably express aberrant fusion proteins involving the retinoic acid receptor alpha (RARalpha). The most common fusion partner is promyelocytic leukemia protein (PML), which is fused to RARalpha in the balanced reciprocal chromosomal translocation, t(15;17)(q22:q11). Expression of PML/RARalpha from the cathepsin G promoter in transgenic mice causes a nonfatal myeloproliferative syndrome in all mice; about 15% go on to develop APL after a long latent period, suggesting that additional mutations are required for the development of APL. A candidate target gene for a second mutation is FLT3, because it is mutated in approximately 40% of human APL cases. Activating mutations in FLT3, including internal tandem duplication (ITD) in the juxtamembrane domain, transform hematopoietic cell lines to factor independent growth. FLT3-ITDs also induce a myeloproliferative disease in a murine bone marrow transplant model, but are not sufficient to cause AML. Here, we test the hypothesis that PML/RARalpha can cooperate with FLT3-ITD to induce an APL-like disease in the mouse. Retroviral transduction of FLT3-ITD into bone marrow cells obtained from PML/RARalpha transgenic mice results in a short latency APL-like disease with complete penetrance. This disease resembles the APL-like disease that occurs with long latency in the PML/RARalpha transgenics, suggesting that activating mutations in FLT3 can functionally substitute for the additional mutations that occur during mouse APL progression. The leukemia is transplantable to secondary recipients and is ATRA responsive. These observations document cooperation between PML/RARalpha and FLT3-ITD in development of the murine APL phenotype.
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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.