ArticleHaematologica2017
Reduced hematopoietic stem cell frequency predicts outcome in acute myeloid leukemia.
Article in Haematologica, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 47 citations in OpenAlex.
- Dysregulation of the Bone Marrow Microenvironment in Pediatric Tumors: The Role of Extracellular Vesicles in Acute Leukemias and Neuroblastoma.International journal of molecular sciences · 2025Review
- Modelling post-chemotherapy stem cell dynamics in the bone marrow niche of AML patients.Scientific reports · 2024Article
- Mathematical modelling of stem and progenitor cell dynamics during ruxolitinib treatment of patients with myeloproliferative neoplasms.Frontiers in immunology · 2024Article
- Identification of Cell Type-Specific Effects ofMolecules and cells · 2023Article
- Bcl-2 inhibition combined with PPARα activation synergistically targets leukemic stem cell-like cells in acute myeloid leukemia.Cell death & disease · 2023Article
- HSC Niche Dynamics in Regeneration, Pre-malignancy, and Cancer: Insights From Mathematical Modeling.Stem cells (Dayton, Ohio) · 2023Article
- An integrative systems biology approach to overcome venetoclax resistance in acute myeloid leukemia.PLoS computational biology · 2022Article
- Local asymptotic stability of a system of integro-differential equations describing clonal evolution of a self-renewing cell population under mutation.Journal of mathematical biology · 2022Article
- Leukemic Stem Cell: A Mini-Review on Clinical Perspectives.Frontiers in oncology · 2022Review
- Targeting Lymphotoxin Beta and Paired Box 5: a potential therapeutic strategy for soft tissue sarcoma metastasis.Cancer cell international · 2021Article
- Computational Reconstruction of Clonal Hierarchies From Bulk Sequencing Data of Acute Myeloid Leukemia Samples.Frontiers in physiology · 2021Article
- Suppression Of Aberrant Activation Of NF-κB Pathway In Drug-resistant Leukemia Stem Cells Contributes To Parthenolide-potentiated Reversal Of Drug Resistance In Leukemia.Journal of Cancer · 2021Article
- Differential response to cytotoxic therapy explains treatment dynamics of acute myeloid leukaemia patients: insights from a mathematical modelling approach.Journal of the Royal Society, Interface · 2020Article
- Ginsenoside Rg1 Inhibits Cell Proliferation and Induces Markers of Cell Senescence in CD34+CD38- Leukemia Stem Cells Derived from KG1α Acute Myeloid Leukemia Cells by Activating the Sirtuin 1 (SIRT1)/Tuberous Sclerosis Complex 2 (TSC2) Signaling Pathway.Medical science monitor : international medical journal of experimental and clinical research · 2020Article
- Identification of leukemia stem cell expression signatures through Monte Carlo feature selection strategy and support vector machine.Cancer gene therapy · 2020Article
- A structured population model of clonal selection in acute leukemias with multiple maturation stages.Journal of mathematical biology · 2019Article
- Mathematical models for cytarabine-derived myelosuppression in acute myeloid leukaemia.PloS one · 2019Article
- A computational model of feedback-mediated hematopoietic stem cell differentiation in vitro.PloS one · 2019Article
Corrections and comments
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Authors and funding
18 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In patients with acute myeloid leukemia and low percentages of aldehyde-dehydrogenase-positive cells, non-leukemic hematopoietic stem cells can be separated from leukemic cells. By relating hematopoietic stem cell frequencies to outcome we detected poor overall- and disease-free survival of patients with low hematopoietic stem cell frequencies. Serial analysis of matched diagnostic and follow-up samples further demonstrated that hematopoietic stem cells increased after chemotherapy in patients who achieved durable remissions. However, in patients who eventually relapsed, hematopoietic stem cell numbers decreased dramatically at the time of molecular relapse demonstrating that hematopoietic stem cell levels represent an indirect marker of minimal residual disease, which heralds leukemic relapse. Upon transplantation in immune-deficient mice cases with low percentages of hematopoietic stem cells of our cohort gave rise to leukemic or no engraftment, whereas cases with normal hematopoietic stem cell levels mostly resulted in multi-lineage engraftment. Based on our experimental data, we propose that leukemic stem cells have increased niche affinity in cases with low percentages of hematopoietic stem cells. To validate this hypothesis, we developed new mathematical models describing the dynamics of healthy and leukemic cells under different regulatory scenarios. These models suggest that the mechanism leading to decreases in hematopoietic stem cell frequencies before leukemic relapse must be based on expansion of leukemic stem cells with high niche affinity and the ability to dislodge hematopoietic stem cells. Thus, our data suggest that decreasing numbers of hematopoietic stem cells indicate leukemic stem cell persistence and the emergence of leukemic relapse.
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