ArticleProceedings of the National Academy of Sciences of the United States of America2015
Reversion to an embryonic alternative splicing program enhances leukemia stem cell self-renewal.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
28 citing papers in PubMed, 44 citations in OpenAlex.
- Functions of the Muscleblind-like protein family and their role in disease.Cell communication and signaling : CCS · 2025Review
- The v8-10 variant isoform of CD44 is selectively expressed in the normal human colonic stem cell niche and frequently is overexpressed in colon carcinomas during tumor development.Cancer biology & therapy · 2023Article
- Stem-Cell Aging and Pathways to Precancer Evolution.The New England journal of medicine · 2023Review
- Development of a Novel Anti-CD44 Variant 8 Monoclonal Antibody CAntibodies (Basel, Switzerland) · 2023Article
- Establishment of a Novel Anti-CD44 Variant 10 Monoclonal Antibody CCurrent issues in molecular biology · 2023Article
- A Novel Anti-CD44 Variant 3 Monoclonal Antibody CInternational journal of molecular sciences · 2023Article
- Detection and targeting of splicing deregulation in pediatric acute myeloid leukemia stem cells.Cell reports. Medicine · 2023Article
- Reversal of malignant ADAR1 splice isoform switching with Rebecsinib.Cell stem cell · 2023Article
- Malignant DFFB isoform switching promotes leukemia survival in relapse pediatric T-cell acute lymphoblastic leukemia.EJHaem · 2023Article
- RNA-binding proteins regulating the CD44 alternative splicing.Frontiers in molecular biosciences · 2023Review
- Article
- CD44: A Multifunctional Mediator of Cancer Progression.Biomolecules · 2021Review
- Splicing Anomalies in Myeloproliferative Neoplasms: Paving the Way for New Therapeutic Venues.Cancers · 2020Review
- Transcriptome profiling reveals the high incidence of hnRNPA1 exon 8 inclusion in chronic myeloid leukemia.Journal of advanced research · 2020Article
- SRSF1 mediates cytokine-induced impaired imatinib sensitivity in chronic myeloid leukemia.Leukemia · 2020Article
- Cell surface GRP78 promotes stemness in normal and neoplastic cells.Scientific reports · 2020Article
- Post-Transcriptional Regulation of Homeostatic, Stressed, and Malignant Stem Cells.Cell stem cell · 2020Review
- Integrative Genomic Analysis Reveals Cancer-Associated Gene Mutations in Chronic Myeloid Leukemia Patients with Resistance or Intolerance to Tyrosine Kinase Inhibitor.OncoTargets and therapy · 2020Article
- Review
- The vascular bone marrow niche influences outcome in chronic myeloid leukemiaHaematologica · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Formative research suggests that a human embryonic stem cell-specific alternative splicing gene regulatory network, which is repressed by Muscleblind-like (MBNL) RNA binding proteins, is involved in cell reprogramming. In this study, RNA sequencing, splice isoform-specific quantitative RT-PCR, lentiviral transduction, and in vivo humanized mouse model studies demonstrated that malignant reprogramming of progenitors into self-renewing blast crisis chronic myeloid leukemia stem cells (BC LSCs) was partially driven by decreased MBNL3. Lentiviral knockdown of MBNL3 resulted in reversion to an embryonic alternative splice isoform program typified by overexpression of CD44 transcript variant 3, containing variant exons 8-10, and BC LSC proliferation. Although isoform-specific lentiviral CD44v3 overexpression enhanced chronic phase chronic myeloid leukemia (CML) progenitor replating capacity, lentiviral shRNA knockdown abrogated these effects. Combined treatment with a humanized pan-CD44 monoclonal antibody and a breakpoint cluster region - ABL proto-oncogene 1, nonreceptor tyrosine kinase (BCR-ABL1) antagonist inhibited LSC maintenance in a niche-dependent manner. In summary, MBNL3 down-regulation-related reversion to an embryonic alternative splicing program, typified by CD44v3 overexpression, represents a previously unidentified mechanism governing malignant progenitor reprogramming in malignant microenvironments and provides a pivotal opportunity for selective BC LSC detection and therapeutic elimination.
Indexed as
Identifiers
What OpenQuestion holds
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.