ArticleBlood2013
Genomic instability may originate from imatinib-refractory chronic myeloid leukemia stem cells.
Article in Blood, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
What it found
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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
75 citing papers in PubMed, 132 citations in OpenAlex.
- Separase activity distribution can be a marker of major molecular response and proliferation of CD34Annals of hematology · 2020Trial
- Intrinsic cellular resistance to BCR::ABL1 inhibitors.Haematologica · 2026Review
- Low initial hemoglobin and high-risk additional chromosomal abnormalities predict poor long-term survival in chronic phase chronic myeloid leukemia.Discover oncology · 2026Article
- Inhibition of Pellino-1 reverts the progression and tyrosine kinase inhibitor resistance in chronic myeloid leukemia.Cell death & disease · 2026Article
- Evolving Therapeutic Algorithms in Chronic Myeloid Leukemia: Integrating Efficacy, Safety, and Survivorship.Biomedicines · 2026Review
- A Gremlin 1-expressing splenic niche cell population restrains chronic myeloid leukemia by antagonizing the BMP pathway.Nature cancer · 2025Article
- Circular RNAJournal of thoracic disease · 2024Article
- Article
- BCR::ABL1 Proteolysis-targeting chimeras (PROTACs): The new frontier in the treatment of PhLeukemia · 2024Review
- Asciminib antagonizes transplantable BCR::ABL1-positive lymphoid blast crisis in vivo by targeting malignant stem cells.Leukemia · 2024Article
- NCellular and molecular life sciences : CMLS · 2024Review
- Antileukemic potential of methylated indolequinone MAC681 through immunogenic necroptosis and PARP1 degradation.Biomarker research · 2024Article
- Impact of additional genetic abnormalities at diagnosis of chronic myeloid leukemia for first-line imatinib-treated patients receiving proactive treatment intervention.Haematologica · 2023Article
- The Interplay between Dysregulated Metabolism and Epigenetics in Cancer.Biomolecules · 2023Review
- Targeting Poly(ADP)ribose polymerase in BCR/ABL1-positive cells.Scientific reports · 2023Article
- DNA Damage Response (DDR) Is Associated With Treatment-free Remission in Chronic Myeloid Leukemia Patients.HemaSphere · 2023Article
- Article
- NOX Dependent ROS Generation and Cell Metabolism.International journal of molecular sciences · 2023Review
- Tyrosine Kinase Inhibitor Independent Gene Expression Signature in CML Offers New Targets for LSPC Eradication Therapy.Cancers · 2022Article
- Properties of Leukemic Stem Cells in Regulating Drug Resistance in Acute and Chronic Myeloid Leukemias.Biomedicines · 2022Review
15 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 10 institutions in 4 countries.
Funding
Abstract
Genomic instability is a hallmark of chronic myeloid leukemia in chronic phase (CML-CP) resulting in BCR-ABL1 mutations encoding resistance to tyrosine kinase inhibitors (TKIs) and/or additional chromosomal aberrations leading to disease relapse and/or malignant progression. TKI-naive and TKI-treated leukemia stem cells (LSCs) and leukemia progenitor cells (LPCs) accumulate high levels of reactive oxygen species (ROS) and oxidative DNA damage. To determine the role of TKI-refractory LSCs in genomic instability, we used a murine model of CML-CP where ROS-induced oxidative DNA damage was elevated in LSCs, including quiescent LSCs, but not in LPCs. ROS-induced oxidative DNA damage in LSCs caused clinically relevant genomic instability in CML-CP-like mice, such as TKI-resistant BCR-ABL1 mutations (E255K, T315I, H396P), deletions in Ikzf1 and Trp53, and additions in Zfp423 and Idh1. Despite inhibition of BCR-ABL1 kinase, imatinib did not downregulate ROS and oxidative DNA damage in TKI-refractory LSCs to the levels detected in normal cells, and CML-CP-like mice treated with imatinib continued to accumulate clinically relevant genetic aberrations. Inhibition of class I p21-activated protein kinases by IPA3 downregulated ROS in TKI-naive and TKI-treated LSCs. Altogether, we postulate that genomic instability may originate in the most primitive TKI-refractory LSCs in TKI-naive and TKI-treated patients.
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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.