ArticleCancer research2016
Aberrant Notch Signaling in the Bone Marrow Microenvironment of Acute Lymphoid Leukemia Suppresses Osteoblast-Mediated Support of Hematopoietic Niche Function.
Article in Cancer research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 47 citations in OpenAlex.
- FGF18 mediates fibroblast-leukemia cross talk to promote acute myeloid leukemia progression.Blood · 2026Article
- Endothelial PERK restricts lymphoid regeneration by reducing DLL4-NOTCH3 signaling at the Pre-B niche.Cell reports · 2026Article
- The Glyco-Switch of life: O-GlcNAcylation in cell fate decision.Glycobiology · 2025Review
- Tumor microenvironment as a novel therapeutic target for lymphoid leukemias.Annals of hematology · 2025Review
- BACH2-mediated CD28 and CD40LG axes contribute to pathogenesis and progression of T-cell lymphoblastic leukemia.Cell death & disease · 2024Article
- AML alters bone marrow stromal cell osteogenic commitment via Notch signaling.Frontiers in immunology · 2023Article
- Targeting Leukemia-Initiating Cells and Leukemic Niches: The Next Therapy Station for T-Cell Acute Lymphoblastic Leukemia?Cancers · 2022Review
- Subversion of Serotonin Receptor Signaling in Osteoblasts by Kynurenine Drives Acute Myeloid Leukemia.Cancer discovery · 2022Article
- Endothelial PERK-ATF4-JAG1 axis activated by T-ALL remodels bone marrow vascular niche.Theranostics · 2022Article
- Notch-Signaling Deregulation Induces Myeloid-Derived Suppressor Cells in T-Cell Acute Lymphoblastic Leukemia.Frontiers in immunology · 2022Article
- Sensitization to Drug Treatment in Precursor B-Cell Acute Lymphoblastic Leukemia Is Not Achieved by Stromal NF-κB Inhibition of Cell Adhesion but by Stromal PKC-Dependent Inhibition of ABC Transporters Activity.Molecules (Basel, Switzerland) · 2021Article
- Nature or Nurture? Role of the Bone Marrow Microenvironment in the Genesis and Maintenance of Myelodysplastic Syndromes.Cancers · 2021Review
- Therapeutic Targeting of the Leukaemia Microenvironment.International journal of molecular sciences · 2021Review
- Notch-Regulated Dendritic Cells Restrain Inflammation-Associated Colorectal Carcinogenesis.Cancer immunology research · 2021Article
- Arhgap21 Deficiency Results in Increase of Osteoblastic Lineage Cells in the Murine Bone Marrow Microenvironment.Frontiers in cell and developmental biology · 2021Article
- Facts and Challenges in Immunotherapy for T-Cell Acute Lymphoblastic Leukemia.International journal of molecular sciences · 2020Review
- The Role of Notch and Wnt Signaling in MSC Communication in Normal and Leukemic Bone Marrow Niche.Frontiers in cell and developmental biology · 2020Review
- The Bone Marrow Niche - The Tumor Microenvironment That Ensures Leukemia Progression.Advances in experimental medicine and biology · 2020Review
- NF-κB1 Regulates Immune Environment and Outcome of Notch-Dependent T-Cell Acute Lymphoblastic Leukemia.Frontiers in immunology · 2020Article
- Vascular Notch Signaling in Stress Hematopoiesis.Frontiers in cell and developmental biology · 2020Review
Corrections and comments
- Erratum issued
Authors and funding
14 authors at 2 institutions in 1 country.
Funding
Abstract
More than half of T-cell acute lymphoblastic leukemia (T-ALL) patients harbor gain-of-function mutations in the intracellular domain of Notch1. Diffuse infiltration of the bone marrow commonly occurs in T-ALL and relapsed B-cell acute lymphoblastic leukemia patients, and is associated with worse prognosis. However, the mechanism of leukemia outgrowth in the marrow and the resulting biologic impact on hematopoiesis are poorly understood. Here, we investigated targetable cellular and molecular abnormalities in leukemia marrow stroma responsible for the suppression of normal hematopoiesis using a T-ALL mouse model and human T-ALL xenografts. We found that actively proliferating leukemia cells inhibited normal hematopoietic stem and progenitor cell (HSPC) proliferation and homing to the perivascular region. In addition, leukemia development was accompanied by the suppression of the endosteum-lining osteoblast population. We further demonstrated that aberrant Notch activation in the stroma plays an important role in negatively regulating the expression of CXLC12 on osteoblasts and their differentiation. Notch blockade reversed attenuated HSPC cycling, leukemia-associated abnormal blood lineage distribution, and thrombocytopenia as well as recovered osteoblast and HSPC abundance and improved the hematopoietic-supportive functions of osteoblasts. Finally, we confirmed that reduced osteoblast frequency and enhanced Notch signaling were also features of the marrow stroma of human ALL tissues. Collectively, our findings suggest that therapeutically targeting the leukemia-infiltrated hematopoietic niche may restore HSPC homeostasis and improve the outcome of ALL patients.
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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.