ArticleScience translational medicine2016
Combined targeting of BCL-2 and BCR-ABL tyrosine kinase eradicates chronic myeloid leukemia stem cells.
Article in Science translational medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers.
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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
95 citing papers in PubMed, 169 citations in OpenAlex.
- Menin Inhibition With Revumenib forJournal of clinical oncology : official journal of the American Society of Clinical Oncology · 2025Trial
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- m6A and NuRD complexes regulate monocytic differentiation and resistance to BCL2/BCL2L1 inhibitors in acute myeloid leukemia.Haematologica · 2026Article
- Multimodal gene and targeted drug therapy for chronic myelogenous leukemia using BIM/MCL-1 chimeric nanoparticle: computational target analysis and therapeutic validation.Nano convergence · 2026Article
- A Novel CIP2A and BCL-XL Clinical Diagnostic Toolkit to Predict Disease Progression and Treatment-Free Remission in Chronic Myeloid Leukaemia.International journal of molecular sciences · 2026Article
- Molecularly targeted therapy and immunotherapy in leukemias.Journal of hematology & oncology · 2026Review
- Unveiling CrypticInternational journal of molecular sciences · 2025Article
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- Chronic inflammation deters natural killer cell fitness and cytotoxicity in myeloid leukemia.Blood advances · 2025Article
- Targeting DDX3X eliminates leukemia stem cells in chronic myeloid leukemia by blocking NT5DC2 mRNA translation.Oncogene · 2025Article
- LIPA-frogging blast phase chronic myeloid leukemia: hopping over resistance with lysosomal targeting.Haematologica · 2025Article
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- Lysosomal acid lipase A modulates leukemia stem cell response to venetoclax/tyrosine kinase inhibitor combination therapy in blast phase chronic myeloid leukemia.Haematologica · 2025Article
- The road not taken: Exploring non-transplant options in De Novo philadelphia positive acute myeloid leukemia.Leukemia research reports · 2025Article
- Novel targeted therapies in chronic myeloid leukemia.Pharmaceutical science advances · 2024Review
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- Integrated functional genomic screening to bypass TKI resistance in chronic myeloid leukemia.Cell reports. Medicine · 2024Article
- Integrated drug profiling and CRISPR screening identify BCR::ABL1-independent vulnerabilities in chronic myeloid leukemia.Cell reports. Medicine · 2024Article
- siRNA-mediated downregulation of BATF3 diminished proliferation and induced apoptosis through downregulating c-Myc expression in chronic myelogenous leukemia cells.Molecular biology reports · 2024Article
35 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
BCR-ABL tyrosine kinase inhibitors (TKIs) are effective against chronic myeloid leukemia (CML), but they rarely eliminate CML stem cells. Disease relapse is common upon therapy cessation, even in patients with complete molecular responses. Furthermore, once CML progresses to blast crisis (BC), treatment outcomes are dismal. We hypothesized that concomitant targeting of BCL-2 and BCR-ABL tyrosine kinase could overcome these limitations. We demonstrate increased BCL-2 expression at the protein level in bone marrow cells, particularly in Lin(-)Sca-1(+)cKit(+) cells of inducible CML in mice, as determined by CyTOF mass cytometry. Further, selective inhibition of BCL-2, aided by TKI-mediated MCL-1 and BCL-XL inhibition, markedly decreased leukemic Lin(-)Sca-1(+)cKit(+) cell numbers and long-term stem cell frequency and prolonged survival in a murine CML model. Additionally, this combination effectively eradicated CD34(+)CD38(-), CD34(+)CD38(+), and quiescent stem/progenitor CD34(+) cells from BC CML patient samples. Our results suggest that BCL-2 is a key survival factor for CML stem/progenitor cells and that combined inhibition of BCL-2 and BCR-ABL tyrosine kinase has the potential to significantly improve depth of response and cure rates of chronic-phase and BC CML.
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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.