ArticleProceedings of the National Academy of Sciences of the United States of America2009
Glycogen synthase kinase 3beta missplicing contributes to leukemia stem cell generation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 135 papers.
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Who cites it
135 citing papers in PubMed, 239 citations in OpenAlex.
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- Nanobioreactor detection of space-associated hematopoietic stem and progenitor cell aging.Cell stem cell · 2025Article
- Adenosine-to-inosine RNA editing in cancer: molecular mechanisms and downstream targets.Protein & cell · 2025Review
- Navigating the Molecular Signaling: Deciphering Cancer Stem Cell Self-Renewal Pathways.International journal of molecular and cellular medicine · 2025Review
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- The Effect of Sargassum Angustifolium-derived AgNPs on Apoptosis-associated Genes in Acute Lymphoblastic Leukemia Cells.Asian Pacific journal of cancer prevention : APJCP · 2023Article
- A-to-I edited miR-411-5p targets MET and promotes TKI response in NSCLC-resistant cells.Oncogene · 2023Article
- Genomic Landscape and Potential Regulation of RNA Editing in Drug Resistance.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
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- 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
- Emerging Roles of Epigenetic Regulators in Maintaining Hematopoietic Stem Cell Homeostasis.Advances in experimental medicine and biology · 2023Article
- Wnt regulation of hematopoietic stem cell development and disease.Current topics in developmental biology · 2023Review
- Loss of G0/G1 switch gene 2 (G0S2) promotes disease progression and drug resistance in chronic myeloid leukaemia (CML) by disrupting glycerophospholipid metabolism.Clinical and translational medicine · 2022Article
- The splicing factor RBM17 drives leukemic stem cell maintenance by evading nonsense-mediated decay of pro-leukemic factors.Nature communications · 2022Article
- Decrypting a path based approach for identifying the interplay between PI3K and GSK3 signaling cascade from the perspective of cancer.Genes & diseases · 2022Review
- Review
75 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 6 institutions in 2 countries.
Funding
Abstract
Recent evidence suggests that a rare population of self-renewing cancer stem cells (CSC) is responsible for cancer progression and therapeutic resistance. Chronic myeloid leukemia (CML) represents an important paradigm for understanding the genetic and epigenetic events involved in CSC production. CML progresses from a chronic phase (CP) in hematopoietic stem cells (HSC) that harbor the BCR-ABL translocation, to blast crisis (BC), characterized by aberrant activation of beta-catenin within granulocyte-macrophage progenitors (GMP). A major barrier to predicting and inhibiting blast crisis transformation has been the identification of mechanisms driving beta-catenin activation. Here we show that BC CML myeloid progenitors, in particular GMP, serially transplant leukemia in immunocompromised mice and thus are enriched for leukemia stem cells (LSC). Notably, cDNA sequencing of Wnt/beta-catenin pathway regulatory genes, including adenomatous polyposis coli, GSK3beta, axin 1, beta-catenin, lymphoid enhancer factor-1, cyclin D1, and c-myc, revealed a novel in-frame splice deletion of the GSK3beta kinase domain in the GMP of BC samples that was not detectable by sequencing in blasts or normal progenitors. Moreover, BC CML progenitors with misspliced GSK3beta have enhanced beta-catenin expression as well as serial engraftment potential while reintroduction of full-length GSK3beta reduces both in vitro replating and leukemic engraftment. We propose that CP CML is initiated by BCR-ABL expression in an HSC clone but that progression to BC may include missplicing of GSK3beta in GMP LSC, enabling unphosphorylated beta-catenin to participate in LSC self-renewal. Missplicing of GSK3beta represents a unique mechanism for the emergence of BC CML LSC and might provide a novel diagnostic and therapeutic target.
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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.