ArticlePloS one2012
NOTCH1 signaling promotes human T-cell acute lymphoblastic leukemia initiating cell regeneration in supportive niches.
Article in PloS one, 2012. 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.
- Deciphering the mechanistic roles of ADARs in cancer pathogenesis, tumor immune evasion, and drug resistance.Frontiers in immunology · 2025Review
- C-C Chemokine Receptor 7 Promotes T-Cell Acute Lymphoblastic Leukemia Invasion of the Central Nervous System via β2-Integrins.International journal of molecular sciences · 2024Article
- Malignant A-to-I RNA editing by ADAR1 drives T cell acute lymphoblastic leukemia relapse via attenuating dsRNA sensing.Cell reports · 2024Article
- Role of epigenetic in cancer biology, in hematologic malignancies and in anticancer therapy.Frontiers in molecular medicine · 2024Review
- Fate of hematopoietic stem cells determined by Notch1 signaling (Review).Experimental and therapeutic medicine · 2022Review
- Oncogene-Induced Reprogramming in Acute Lymphoblastic Leukemia: Towards Targeted Therapy of Leukemia-Initiating Cells.Cancers · 2021Review
- Cancer Stem Cells,Cells · 2020Review
- Surfaceome interrogation using an RNA-seq approach highlights leukemia initiating cell biomarkers in an LMO2 T cell transgenic model.Scientific reports · 2019Article
- Re-establishing Apoptosis Competence in Bone Associated Cancers via Communicative Reprogramming Induced Through Notch Signaling Inhibition.Frontiers in pharmacology · 2019Review
- Alu-dependent RNA editing of GLI1 promotes malignant regeneration in multiple myeloma.Nature communications · 2017Article
- Multiple myeloma-derived Jagged ligands increases autocrine and paracrine interleukin-6 expression in bone marrow niche.Oncotarget · 2016Article
- Targeting leukemia stem cells: which pathways drive self-renewal activity in T-cell acute lymphoblastic leukemia?Current oncology (Toronto, Ont.) · 2016Review
- A novel Monoclonal Antibody against Notch1 Targets Leukemia-associated Mutant Notch1 and Depletes Therapy Resistant Cancer Stem Cells in Solid Tumors.Scientific reports · 2015Article
- Mechanisms determining the fate of hematopoietic stem cells.Stem cell investigation · 2015Review
- PCSD1, a new patient-derived model of bone metastatic prostate cancer, is castrate-resistant in the bone-niche.Journal of translational medicine · 2014Article
- Article
- Therapeutic antibody targeting of Notch1 in T-acute lymphoblastic leukemia xenografts.Leukemia · 2014Article
- The emerging roles of Notch signaling in leukemia and stem cells.Biomarker research · 2013Article
Corrections and comments
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Authors and funding
20 authors.
Funding
Abstract
backgroundLeukemia initiating cells (LIC) contribute to therapeutic resistance through acquisition of mutations in signaling pathways, such as NOTCH1, that promote self-renewal and survival within supportive niches. Activating mutations in NOTCH1 occur commonly in T cell acute lymphoblastic leukemia (T-ALL) and have been implicated in therapeutic resistance. However, the cell type and context specific consequences of NOTCH1 activation, its role in human LIC regeneration, and sensitivity to NOTCH1 inhibition in hematopoietic microenvironments had not been elucidated. METHODOLOGY AND PRINCIPAL
findingsWe established humanized bioluminescent T-ALL LIC mouse models transplanted with pediatric T-ALL samples that were sequenced for NOTCH1 and other common T-ALL mutations. In this study, CD34(+) cells from NOTCH1(Mutated) T-ALL samples had higher leukemic engraftment and serial transplantation capacity than NOTCH1(Wild-type) CD34(+) cells in hematopoietic niches, suggesting that self-renewing LIC were enriched within the NOTCH1(Mutated) CD34(+) fraction. Humanized NOTCH1 monoclonal antibody treatment reduced LIC survival and self-renewal in NOTCH1(Mutated) T-ALL LIC-engrafted mice and resulted in depletion of CD34(+)CD2(+)CD7(+) cells that harbor serial transplantation capacity.
conclusionsThese results reveal a functional hierarchy within the LIC population based on NOTCH1 activation, which renders LIC susceptible to targeted NOTCH1 inhibition and highlights the utility of NOTCH1 antibody targeting as a key component of malignant stem cell eradication strategies.
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