ArticleProceedings of the National Academy of Sciences of the United States of America2020
Combined loss of function of two different loci of miR-15/16 drives the pathogenesis of acute myeloid leukemia.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 39 citations in OpenAlex.
- What does BCL-2 do? From new molecular insights to the clinical implications.Cell death and differentiation · 2026Review
- Diagnostic accuracy of circulating miR-146, miR-221 and miR-222 in papillary thyroid cancer: A systematic review and meta-analysis.World journal of clinical cases · 2025Article
- Therapeutic advances in the targeting of ROR1 in hematological cancers.Cell death discovery · 2024Review
- miR-15a targets the HSP90 co-chaperone Morgana in chronic myeloid leukemia.Scientific reports · 2024Article
- Non-coding RNAs as therapeutic targets in cancer and its clinical application.Journal of pharmaceutical analysis · 2024Review
- Combined Delivery of miR-15/16 through Humanized Ferritin Nanocages for the Treatment of Chronic Lymphocytic Leukemia.Pharmaceutics · 2024Article
- Complete miRNA-15/16 loss in mice promotes hematopoietic progenitor expansion and a myeloid-biased hyperproliferative state.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Article
- Effects of miR-33 Deficiency on Metabolic and Cardiovascular Diseases: Implications for Therapeutic Intervention.International journal of molecular sciences · 2023Review
- Crosstalk between Noncoding RNAs and the Epigenetics Machinery in Pediatric Tumors and Their Microenvironment.Cancers · 2023Review
- A miRNA screening identifies miR-192-5p as associated with response to azacitidine and lenalidomide therapy in myelodysplastic syndromes.Clinical epigenetics · 2023Article
- Optimized workflow to modify microRNA expression in primary human intravascular cells.BMC immunology · 2023Article
- The Mechanism of miR-155/miR-15b Axis Contributed to Apoptosis of CD34+ Cells by Upregulation of PD-L1 in Myelodysplastic Syndromes.Mediterranean journal of hematology and infectious diseases · 2023Article
- RNAi-Based Therapeutics and Novel RNA Bioengineering Technologies.The Journal of pharmacology and experimental therapeutics · 2023Review
- MicroRNA-15a-5p acts as a tumor suppressor in histiocytosis by mediating CXCL10-ERK-LIN28a-let-7 axis.Leukemia · 2022Article
- Small Non-Coding RNAs in Leukemia.Cancers · 2022Review
- Glutamine-Derived Aspartate Biosynthesis in Cancer Cells: Role of Mitochondrial Transporters and New Therapeutic Perspectives.Cancers · 2022Review
- microRNA-based diagnostic and therapeutic applications in cancer medicine.Wiley interdisciplinary reviews. RNA · 2021Review
- Non-coding RNA in cancer.Essays in biochemistry · 2021Review
- Current Views on the Interplay between Tyrosine Kinases and Phosphatases in Chronic Myeloid Leukemia.Cancers · 2021Review
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Authors and funding
15 authors at 5 institutions in 3 countries.
Funding
Abstract
Double knockout of the two miR-15/16 loci in mouse resulted in the development of acute myeloid leukemia (AML). This result suggested that, at least, a fraction of human AMLs could be due to a similar mechanism. We analyzed the role of the two miR-15/16 clusters in 93 myelodysplastic syndrome (MDS) patients divided in three subgroups: patients with MDS, patients with MDS before transforming into AML (MDS-T), and patients with AML evolving from MDS (MDS-AML). Then, we tested 139 AML cases and 14 different AML cell lines by assessing microRNA (miRNA) expression, target protein expression, genetic loss, and silencing. MDS-T and MDS-AML patients show a reduction of the expression of miR-15a/-15b/-16 compared to MDS patients. Each miRNA can significantly predict MDS and MDS-T groups. Then, 79% of primary AMLs show a reduced expression of miR-15a and/or miR-15b. The expression of miR-15a/-15b/-16 significantly stratified AML patients in two prognostic classes. Furthermore, 40% of AML cell lines showed a combined loss of the expression of miR-15a/-15b and overexpression of their direct/indirect targets. As potential mechanisms involved in the silencing of the two miR-15/16 loci, we identified a genetic loss of miR-15a and miR-15b and silencing of these two loci by methylation. We identified a potential driver oncogenic role in the loss of expression of both miR-15/16 clusters in the progression of MDS into AML and in AML pathogenesis. The stratification of AML patients, based on miR-15/16 expression, can lead to targeted and combination therapies for the treatment of this incurable disease.
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