ArticleProceedings of the National Academy of Sciences of the United States of America2018
Knockout of both miR-15/16 loci induces acute myeloid leukemia.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 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.
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Who cites it
32 citing papers in PubMed, 49 citations in OpenAlex.
- Article
- A tumor suppressor role of the miR-15b/16-2 cluster in T-cell acute lymphoblastic leukemia.Blood · 2026Article
- What does BCL-2 do? From new molecular insights to the clinical implications.Cell death and differentiation · 2026Review
- microRNA-15b modulates stress-induced premature senescence in chronic doxorubicin cardiomyopathy.Frontiers in pharmacology · 2026Article
- The miR-16-1-3p passenger strand exhibits functional activity and suppresses malignant phenotypes in osteosarcoma.Frontiers in genetics · 2026Article
- miR-221 activates Sox11 to reduce brain injury after intracerebral hemorrhage via inhibiting neuroinflammation.Scientific reports · 2025Article
- Nutrient restriction-activated Fra-2 promotes tumor progression via IGF1R in miR-15a downmodulated pancreatic ductal adenocarcinoma.Signal transduction and targeted therapy · 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
- miRNA in Molecular Diagnostics.Bioengineering (Basel, Switzerland) · 2022Review
- miR-16-5p Is a Novel Mediator of Venous Smooth Muscle Phenotypic Switching.Journal of cardiovascular translational research · 2022Article
- Context-Dependent Regulation of Gene Expression by Non-Canonical Small RNAs.Non-coding RNA · 2022Review
- MicroRNA-15a-5p acts as a tumor suppressor in histiocytosis by mediating CXCL10-ERK-LIN28a-let-7 axis.Leukemia · 2022Article
- Review
- Small Non-Coding RNAs in Leukemia.Cancers · 2022Review
- Tumor Suppressor microRNAs in Gastrointestinal Cancers: A Mini-Review.Recent advances in inflammation & allergy drug discovery · 2022Review
- The miR-15a/16-1 and miR-15b/16-2 clusters regulate early B cell development by limiting IL-7 receptor expression.Frontiers in immunology · 2022Article
- Making Sense of Antisense Oligonucleotide Therapeutics Targeting Bcl-2.Pharmaceutics · 2022Review
- microRNA-based diagnostic and therapeutic applications in cancer medicine.Wiley interdisciplinary reviews. RNA · 2021Review
- Sarcopenia-derived exosomal micro-RNA 16-5p disturbs cardio-repair via a pro-apoptotic mechanism in myocardial infarction in mice.Scientific reports · 2021Article
- Loss of expression of both miR-15/16 loci in CML transition to blast crisis.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 2 countries.
Funding
Abstract
MicroRNAs (miRNAs) have been extensively reported to be associated with hematological malignancies. The loss of miR-15a/16-1 at chromosome 13q14 is a hallmark of most of human chronic lymphocytic leukemia (CLL). Deletion of murine miR-15a/16-1 and miR-15b/16-2 has been demonstrated to promote B cell malignancies. Here, we evaluate the biological role of miR-15/16 clusters, crossbreeding miR-15a/16-1 and miR-15b/16-2 knockout mice. Unexpectedly, the complete deletion of both clusters promoted myeloproliferative disorders in the majority of the mice by the age of 5 months with a penetrance of 70%. These mice showed a significant enlargement of spleen and abnormal swelling of lymph nodes. Flow cytometry characterization demonstrated an expanded CD11b/Gr-1 double-positive myeloid population both in spleen and in bone marrow. The transplantation of splenocytes harvested from double-KO mice into wild-type recipient mice resulted in the development of myeloproliferative disorders, as observed in the donors. In vivo, miR-15/16 cluster deletion up-regulated the expression of Cyclin D1, Cyclin D2, and Bcl-2. Taken together, our findings identify a driver oncogenic role for miR-15/16 cluster deletion in different leukocytic cell lineages.
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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.