ArticleLeukemia2021
Metabolic alterations mediated by STAT3 promotes drug persistence in CML.
Article in Leukemia, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 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.
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Who cites it
35 citing papers in PubMed, 53 citations in OpenAlex.
- Cancer drug response and resistance: molecular mechanisms and combating strategies.Signal transduction and targeted therapy · 2026Review
- Application of NanoString Technologies in Chronic Myeloid Leukemia, Essential Thrombocythemia, Primary Myelofibrosis, and Polycythemia Vera: A Pilot Study.Diagnostics (Basel, Switzerland) · 2026Article
- GOLDEN fusion: a graph-oriented learning with domain-embedding network fusion for generating super gene sets in functional genomics.Briefings in bioinformatics · 2026Article
- Targeting Mitochondrial Vulnerabilities in Chronic Myeloid Leukemia: From Pathobiology to Novel Therapeutic Opportunities.Cancers · 2026Review
- IL21-STAT3 controls the pentose phosphate pathway to support metabolic reprogramming and tumor progression in chronic lymphocytic leukemia.HemaSphere · 2026Article
- PD-L1 Expression in Acute Myeloid Leukemia Cells: Associations With Cell Metabolism.Journal of immunology research · 2026Article
- High-Throughput Metabolomics in Transfusion Medicine.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Review
- Research on the functions and potential mechanisms of STAT3 in chronic myelogenous leukemia.Discover oncology · 2025Article
- circ0066187 promotes pulmonary fibrogenesis through targeting STAT3-mediated metabolism signal pathway.Cellular and molecular life sciences : CMLS · 2025Article
- RNA-binding proteins as versatile metabolic regulators.npj metabolic health and disease · 2025Article
- ZFAS1/STAT3 axis modulates imatinib resistance of chronic myeloid leukemia cells through glucose metabolism reprogramming.Frontiers in oncology · 2025Article
- Biological Features of KLC2 Mutations in Chronic Myeloid Leukemia and Their Contribution to Inducing Drug Resistance.Oncology research · 2025Article
- Chiglitazar diminishes the warburg effect through PPARγ/mTOR/PKM2 and increases the sensitivity of imatinib in chronic myeloid leukemia.Experimental hematology & oncology · 2024Article
- Low Renalase Levels in Newly Diagnosed CML: Dysregulation Sensitive to Modulation by Tyrosine Kinase Inhibitors.Pathophysiology : the official journal of the International Society for Pathophysiology · 2024Article
- Respiratory Virus-Induced PARP1 Alters DC Metabolism and Antiviral Immunity Inducing Pulmonary Immunopathology.Viruses · 2024Article
- CD302 predicts achievement of deep molecular response in patients with chronic myeloid leukemia treated with imatinib.Blood neoplasia · 2024Article
- Antileukemic potential of methylated indolequinone MAC681 through immunogenic necroptosis and PARP1 degradation.Biomarker research · 2024Article
- Metabolic Changes during In Vivo Maturation of PSC-Derived Skeletal Myogenic Progenitors.Cells · 2023Article
- AMPK-induced novel phosphorylation of RUNX1 inhibits STAT3 activation and overcome imatinib resistance in chronic myelogenous leukemia (CML) subjects.Cell death discovery · 2023Article
Corrections and comments
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Authors and funding
24 authors at 7 institutions in 2 countries.
Funding
Abstract
Leukemic stem cells (LSCs) can acquire non-mutational resistance following drug treatment leading to therapeutic failure and relapse. However, oncogene-independent mechanisms of drug persistence in LSCs are incompletely understood, which is the primary focus of this study. We integrated proteomics, transcriptomics, and metabolomics to determine the contribution of STAT3 in promoting metabolic changes in tyrosine kinase inhibitor (TKI) persistent chronic myeloid leukemia (CML) cells. Proteomic and transcriptional differences in TKI persistent CML cells revealed BCR-ABL-independent STAT3 activation in these cells. While knockout of STAT3 inhibited the CML cells from developing drug-persistence, inhibition of STAT3 using a small molecule inhibitor sensitized the persistent CML cells to TKI treatment. Interestingly, given the role of phosphorylated STAT3 as a transcription factor, it localized uniquely to genes regulating metabolic pathways in the TKI-persistent CML stem and progenitor cells. Subsequently, we observed that STAT3 dysregulated mitochondrial metabolism forcing the TKI-persistent CML cells to depend on glycolysis, unlike TKI-sensitive CML cells, which are more reliant on oxidative phosphorylation. Finally, targeting pyruvate kinase M2, a rate-limiting glycolytic enzyme, specifically eradicated the TKI-persistent CML cells. By exploring the role of STAT3 in altering metabolism, we provide critical insight into identifying potential therapeutic targets for eliminating TKI-persistent LSCs.
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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.