ArticleCell stem cell2013
A Pan-BCL2 inhibitor renders bone-marrow-resident human leukemia stem cells sensitive to tyrosine kinase inhibition.
Article in Cell stem cell, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 127 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
127 citing papers in PubMed, 193 citations in OpenAlex.
- Venetoclax for elderly patients with acute myeloid leukaemia unfit for intensive chemotherapy: Prospects, resistance mechanisms and management strategies.Clinical and translational medicine · 2026Review
- Re-evaluating the rationale for targeting oxidative phosphorylation in acute myeloid leukemia.The Biochemical journal · 2026Review
- Targeting the BCR::ABL1 Kinase: Advances Beyond Imatinib in Chronic Myeloid Leukemia.Current hematologic malignancy reports · 2026Review
- 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
- Superior response and survival of intensive chemotherapy over venetoclax plus azacitidine in newly diagnosed KIT-mutated acute myeloid leukemia.Annals of hematology · 2026Article
- Therapeutic Targets for Overcoming BCR::ABL1 Tyrosine Kinase Inhibitor Resistance in Chronic Myeloid Leukemia.Oncology research · 2026Review
- Targeting Osteoclastogenesis: Sabutoclax reduces tumor-associated osteolysis and tumor burden within the bone microenvironment.American journal of cancer research · 2026Article
- Space-associated stem cell hallmarks of aging and resilience in astronauts.Cell stem cell · 2025Article
- Nanobioreactor detection of space-associated hematopoietic stem and progenitor cell aging.Cell stem cell · 2025Article
- Review
- LIPA-frogging blast phase chronic myeloid leukemia: hopping over resistance with lysosomal targeting.Haematologica · 2025Article
- CAR-T cell combination therapies in hematologic malignancies.Experimental hematology & oncology · 2024Review
- Integrated functional genomic screening to bypass TKI resistance in chronic myeloid leukemia.Cell reports. Medicine · 2024Article
- Exploring the therapeutic potential of precision T-Cell Receptors (TCRs) in targeting KRAS G12D cancer throughOncology research · 2024Article
- Integrative genomic analyses combined with molecular dynamics simulations reveal the impact of deleterious mutations of Bcl-2 gene on the apoptotic machinery and implications in carcinogenesis.Frontiers in genetics · 2024Article
- Stem-Cell Aging and Pathways to Precancer Evolution.The New England journal of medicine · 2023Review
- 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
- α‑hederin overcomes hypoxia‑mediated drug resistance in colorectal cancer by inhibiting the AKT/Bcl2 pathway.International journal of oncology · 2023Article
- Malignant DFFB isoform switching promotes leukemia survival in relapse pediatric T-cell acute lymphoblastic leukemia.EJHaem · 2023Article
67 more citing papers are in PubMed but not listed here.
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Authors and funding
35 authors at 9 institutions in 3 countries.
Funding
Abstract
Leukemia stem cells (LSCs) play a pivotal role in the resistance of chronic myeloid leukemia (CML) to tyrosine kinase inhibitors (TKIs) and its progression to blast crisis (BC), in part, through the alternative splicing of self-renewal and survival genes. To elucidate splice-isoform regulators of human BC LSC maintenance, we performed whole-transcriptome RNA sequencing, splice-isoform-specific quantitative RT-PCR (qRT-PCR), nanoproteomics, stromal coculture, and BC LSC xenotransplantation analyses. Cumulatively, these studies show that the alternative splicing of multiple prosurvival BCL2 family genes promotes malignant transformation of myeloid progenitors into BC LSCS that are quiescent in the marrow niche and that contribute to therapeutic resistance. Notably, sabutoclax, a pan-BCL2 inhibitor, renders marrow-niche-resident BC LSCs sensitive to TKIs at doses that spare normal progenitors. These findings underscore the importance of alternative BCL2 family splice-isoform expression in BC LSC maintenance and suggest that the combinatorial inhibition of prosurvival BCL2 family proteins and BCR-ABL may eliminate dormant LSCs and obviate resistance.
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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.