ArticleCell death and differentiation2019
Recipient BCL2 inhibition and NK cell ablation form part of a reduced intensity conditioning regime that improves allo-bone marrow transplantation outcomes.
Article in Cell death and differentiation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 2 of them syntheses that pooled it.
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Who cites it
12 citing papers in PubMed, 2 syntheses or guidelines pooled it, 14 citations in OpenAlex.
- Evolving Paradigms in Chronic Graft-Versus-Host Disease: From Global Immunosuppression to Precision Targeted and Cell-Based Therapies.Stem cell reviews and reports · 2026Pooled it
- Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia: An Overview of Systematic Reviews.International journal of clinical practice · 2022Pooled it
- Synergistic venetoclax and anti-CD3 therapy for control of alloreactive response in hematopoietic stem cell transplantation.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2026Article
- Venetoclax therapy in chronic lymphocytic leukaemia patients relapsed after allogeneic haematopoietic stem cell transplantation.British journal of haematology · 2025Article
- [Efficacy and safety of venetoclax combined with decitabine, modified HA regimen and DLI in the treatment of relapsed pediatric AML/MDS after allogeneic hematopoietic stem cell transplantation].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2024Article
- Smart Conditioning with Venetoclax-Enhanced Sequential FLAMSA + RIC in Patients with High-Risk Myeloid Malignancies.Cancers · 2024Article
- Article
- Pediatric multicellular tumor spheroid models illustrate a therapeutic potential by combining BH3 mimetics with Natural Killer (NK) cell-based immunotherapy.Cell death discovery · 2022Article
- Emerging roles of the HECT-type E3 ubiquitin ligases in hematological malignancies.Discover oncology · 2021Review
- Treatment of AML Relapse After Allo-HCT.Frontiers in oncology · 2021Review
- Venetoclax or Ruxolitinib in Pre-Transplant Conditioning Lowers the Engraftment Barrier by Different Mechanisms in Allogeneic Stem Cell Transplant Recipients.Frontiers in immunology · 2021Article
- Impacts of exercise interventions on different diseases and organ functions in mice.Journal of sport and health science · 2020Review
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 3 countries.
Funding
Abstract
Allogeneic hematopoietic stem cell transplantation (alloSCT) is used to treat over 15,000 patients with acute myeloid leukemia (AML) per year. Donor graft-versus-leukemia (GVL) effect can prevent AML relapse; however, alloSCT is limited by significant toxicity related to conditioning intensity, immunosuppression, opportunistic infections, and graft-versus-host disease (GVHD). Reducing the intensity of conditioning regimens prior to alloSCT has improved their tolerability, but does not alter the pattern of GVHD and has been associated with increased rates of graft rejection and relapse. Here, using a murine pre-clinical model, we describe a novel recipient conditioning approach combining reduced intensity conditioning with either genetic or pharmacological inhibition of NK cell numbers that permits efficient donor engraftment and promotes GVL without inducing GVHD. We show that NK cell-specific deletion of Bcl2 or Mcl1 in mice, or pharmacological inhibition of BCL2 impairs radio-resistant NK cell-mediated rejection of allogeneic engraftment and allows reduction of conditioning intensity below that associated with GVHD priming. The combination of reduced intensity conditioning and NK cell targeting in mice allowed successful donor T cell engraftment and protective immunity against AML while avoiding GVHD. These findings suggest that reduced conditioning in combination with targeted therapies against recipient NK cells may allow the delivery of effective alloSCT against AML while reducing the toxicities associated with more intensive conditioning including GVHD.
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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.