ArticleLeukemia2021
Cytoplasmic DROSHA and non-canonical mechanisms of MiR-155 biogenesis in FLT3-ITD acute myeloid leukemia.
Article in Leukemia, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 9 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
9 citing papers in PubMed, 16 citations in OpenAlex.
- Allosteric inhibition of RAN decreases miR-126 biogenesis in endothelial cells and controls acute myeloid leukemia growth.Communications biology · 2026Article
- Diagnostic and Prognostic Significance of miR-155, miR-181, miR-221, miR-222, and miR-223 Expression in Myelodysplastic Syndromes and Acute Myeloid Leukemia.Diagnostics (Basel, Switzerland) · 2025Article
- Recent advances in drug delivery and treatment strategies for acute myeloid leukemia.International journal of pharmaceutics · 2025Review
- Association ofCurrent issues in molecular biology · 2025Article
- BMPMDA: Prediction of MiRNA-Disease Associations Using a Space Projection Model Based on Block Matrix.Interdisciplinary sciences, computational life sciences · 2023Article
- RNA binding proteins in MLL-rearranged leukemia.Experimental hematology & oncology · 2022Review
- MicroRNA networks in FLT3-ITD acute myeloid leukemia.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Targeting miR-126 in inv(16) acute myeloid leukemia inhibits leukemia development and leukemia stem cell maintenance.Nature communications · 2021Article
- Splice and Dice: Intronic microRNAs, Splicing and Cancer.Biomedicines · 2021Review
Corrections and comments
- Erratum issued
Authors and funding
21 authors at 3 institutions in 1 country.
Funding
Abstract
We report here on a novel pro-leukemogenic role of FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) that interferes with microRNAs (miRNAs) biogenesis in acute myeloid leukemia (AML) blasts. We showed that FLT3-ITD interferes with the canonical biogenesis of intron-hosted miRNAs such as miR-126, by phosphorylating SPRED1 protein and inhibiting the "gatekeeper" Exportin 5 (XPO5)/RAN-GTP complex that regulates the nucleus-to-cytoplasm transport of pre-miRNAs for completion of maturation into mature miRNAs. Of note, despite the blockage of "canonical" miRNA biogenesis, miR-155 remains upregulated in FLT3-ITD+ AML blasts, suggesting activation of alternative mechanisms of miRNA biogenesis that circumvent the XPO5/RAN-GTP blockage. MiR-155, a BIC-155 long noncoding (lnc) RNA-hosted oncogenic miRNA, has previously been implicated in FLT3-ITD+ AML blast hyperproliferation. We showed that FLT3-ITD upregulates miR-155 by inhibiting DDX3X, a protein implicated in the splicing of lncRNAs, via p-AKT. Inhibition of DDX3X increases unspliced BIC-155 that is then shuttled by NXF1 from the nucleus to the cytoplasm, where it is processed into mature miR-155 by cytoplasmic DROSHA, thereby bypassing the XPO5/RAN-GTP blockage via "non-canonical" mechanisms of miRNA biogenesis.
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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.