ArticleOncotarget2015
Stromal cell-mediated mitochondrial redox adaptation regulates drug resistance in childhood acute lymphoblastic leukemia.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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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.
The trial behind it
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Who cites it
21 citing papers in PubMed, 30 citations in OpenAlex.
- Functional precision approach in patients with very high risk acute lymphoblastic leukaemia in India: a single-centre cohort study.The Lancet regional health. Southeast Asia · 2026Article
- Pitavastatin Is Anti-Leukemic in a Bone Marrow Microenvironment Model of B-Lineage Acute Lymphoblastic Leukemia.Cancers · 2022Article
- Bone Marrow Aging and the Leukaemia-Induced Senescence of Mesenchymal Stem/Stromal Cells: Exploring Similarities.Journal of personalized medicine · 2022Review
- Leukemia-Induced Cellular Senescence and Stemness Alterations in Mesenchymal Stem Cells Are Reversible upon Withdrawal of B-Cell Acute Lymphoblastic Leukemia Cells.International journal of molecular sciences · 2021Article
- Redox Control in Acute Lymphoblastic Leukemia: From Physiology to Pathology and Therapeutic Opportunities.Cells · 2021Review
- Impact of the induction phase chemotherapy on cytokines and oxidative markers in peripheral and bone marrow plasma of children with acute lymphocytic leukemia.Current research in immunology · 2021Article
- CD81 knockout promotes chemosensitivity and disrupts in vivo homing and engraftment in acute lymphoblastic leukemia.Blood advances · 2020Article
- Bone marrow niches in haematological malignancies.Nature reviews. Cancer · 2020Review
- Oxidative resistance of leukemic stem cells and oxidative damage to hematopoietic stem cells under pro-oxidative therapy.Cell death & disease · 2020Review
- Review
- Dynamic responses of the haematopoietic stem cell niche to diverse stresses.Nature cell biology · 2020Review
- The Metabolic Profiles in Hematological Malignancies.Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion · 2019Review
- A rare subgroup of leukemia stem cells harbors relapse-inducing potential in acute lymphoblastic leukemia.Experimental hematology · 2019Review
- Jab1/Csn5-Thioredoxin Signaling in Relapsed Acute Monocytic Leukemia under Oxidative Stress.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Article
- New insights into redox homeostasis as a therapeutic target in B-cell malignancies.Current opinion in hematology · 2017Review
- Targeting the 5T4 oncofetal glycoprotein with an antibody drug conjugate (A1mcMMAF) improves survival in patient-derived xenograft models of acute lymphoblastic leukemia.Haematologica · 2017Article
- Eviction from the sanctuary: Development of targeted therapy against cell adhesion molecules in acute lymphoblastic leukemia.Seminars in oncology · 2017Review
- Review
- Acute lymphoblastic leukaemia cells produce large extracellular vesicles containing organelles and an active cytoskeleton.Journal of extracellular vesicles · 2017Article
- Differential regulation of cell death pathways by the microenvironment correlates with chemoresistance and survival in leukaemia.PloS one · 2017Article
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 2 countries.
Funding
Abstract
Despite the high cure rates in childhood acute lymphoblastic leukemia (ALL), relapsed ALL remains a significant clinical problem. Genetic heterogeneity does not adequately explain variations in response to therapy. The chemoprotective tumor microenvironment may additionally contribute to disease recurrence. This study identifies metabolic reprogramming of leukemic cells by bone marrow stromal cells (BMSC) as a putative mechanism of drug resistance. In a BMSC-extracellular matrix culture model, BMSC produced chemoprotective soluble factors and facilitated the emergence of a reversible multidrug resistant phenotype in ALL cells. BMSC environment induced a mitochondrial calcium influx leading to increased reactive oxygen species (ROS) levels in ALL cells. In response to this oxidative stress, drug resistant cells underwent a redox adaptation process, characterized by a decrease in ROS levels and mitochondrial membrane potential with an upregulation of antioxidant production and MCL-1 expression. Similar expanded subpopulations of low ROS expressing and drug resistant cells were identified in pre-treatment bone marrow samples from ALL patients with slower response to therapy. This suggests that the bone marrow microenvironment induces a redox adaptation in ALL subclones that protects against cytotoxic stress and potentially gives rise to minimal residual disease. Targeting metabolic remodeling by inhibiting antioxidant production and antiapoptosis was able to overcome drug resistance. Thus metabolic plasticity in leukemic cell response to environmental factors contributes to chemoresistance and disease recurrence. Adjunctive strategies targeting such processes have the potential to overcome therapeutic failure in ALL.
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Registered trials
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