ArticleCancer research2016
Acute Sensitivity of Ph-like Acute Lymphoblastic Leukemia to the SMAC-Mimetic Birinapant.
Article in Cancer research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 21 citations in OpenAlex.
- Article
- Targeting the TNF/IAP pathway synergizes with anti-CD3 immunotherapy in T-cell acute lymphoblastic leukemia.Blood · 2024Article
- Definition and Prognostic Value of Ph-like and IKZF1plus Status in Children With Down Syndrome and B-cell Precursor Acute Lymphoblastic Leukemia.HemaSphere · 2023Article
- Philadelphia-like acute lymphoblastic leukemia: the journey from molecular background to the role of bone marrow transplant-review article.Annals of hematology · 2023Review
- X-linked inhibitor of apoptosis protein represents a promising therapeutic target for relapsed/refractory ALL.EMBO molecular medicine · 2023Article
- TNFR2 is required for RIP1-dependent cell death in human leukemia.Blood advances · 2020Article
- Combinatorial Treatment of Birinapant and Zosuquidar Enhances Effective Control of HBV Replication In Vivo.Viruses · 2020Article
- The Current Genomic and Molecular Landscape of Philadelphia-like Acute Lymphoblastic Leukemia.International journal of molecular sciences · 2020Review
- The Immuno-Modulatory Effects of Inhibitor of Apoptosis Protein Antagonists in Cancer Immunotherapy.Cells · 2020Review
- Exploiting Necroptosis for Therapy of Acute Lymphoblastic Leukemia.Frontiers in cell and developmental biology · 2019Review
- Necroinflammation emerges as a key regulator of hematopoiesis in health and disease.Cell death and differentiation · 2019Review
- Dysregulation of BCL-2 family proteins by leukemia fusion genes.The Journal of biological chemistry · 2017Review
- Philadelphia-Like Acute Lymphoblastic Leukemia in Adults.Current oncology reports · 2017Review
Corrections and comments
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Authors and funding
15 authors at 7 institutions in 2 countries.
Funding
Abstract
Ph-like acute lymphoblastic leukemia (ALL) is a genetically defined high-risk ALL subtype with a generally poor prognosis. In this study, we evaluated the efficacy of birinapant, a small-molecule mimetic of the apoptotic regulator SMAC, against a diverse set of ALL subtypes. Birinapant exhibited potent and selective cytotoxicity against B-cell precursor ALL (BCP-ALL) cells that were cultured ex vivo or in vivo as patient-derived tumor xenografts (PDX). Cytotoxicity was consistently most acute in Ph-like BCP-ALL. Unbiased gene expression analysis of BCP-ALL PDX specimens identified a 68-gene signature associated with birinapant sensitivity, including an enrichment for genes involved in inflammatory response, hematopoiesis, and cell death pathways. All Ph-like PDXs analyzed clustered within this 68-gene classifier. Mechanistically, birinapant sensitivity was associated with expression of TNF receptor TNFR1 and was abrogated by interfering with the TNFα/TNFR1 interaction. In combination therapy, birinapant enhanced the in vivo efficacy of an induction-type regimen of vincristine, dexamethasone, and L-asparaginase against Ph-like ALL xenografts, offering a preclinical rationale to further evaluate this SMAC mimetic for BCP-ALL treatment. Cancer Res; 76(15); 4579-91. ©2016 AACR.
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