ArticleBlood cancer journal2014
A pre-clinical model of resistance to induction therapy in pediatric acute lymphoblastic leukemia.
Article in Blood cancer journal, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- The Influence of Statin Use on Chemotherapeutic Efficacy in Studies of Mouse Models: A Systematic Review.Anticancer research · 2023Pooled it
- Central nervous system involvement in acute lymphoblastic leukemia: pathogenesis and targeted therapy.Leukemia · 2026Review
- MYC Addiction as a Targetable Vulnerability in Nelarabine-Resistant T-Cell Acute Lymphoblastic Leukemia.Cancer science · 2026Article
- Establishment and characterization of a novel cell line ICH-BCPALL-3 from B cell precursor acute lymphoblastic leukemia with TCF3::HLF.Human cell · 2025Article
- High CD44 expression and enhanced E-selectin binding identified as biomarkers of chemoresistant leukemic cells in human T-ALL.Leukemia · 2025Article
- Integrated multi-omics analyses reveal homology-directed repair pathway as a unique dependency in near-haploid leukemia.Blood cancer journal · 2023Article
- CCR9 overexpression promotes T-ALL progression by enhancing cholesterol biosynthesis.Frontiers in pharmacology · 2023Article
- Article
- More Related Gene Pathways to Vincristine-Induced Death Events in a Human T-Acute Lymphoblastic Leukemia Cell Line.Reports of biochemistry & molecular biology · 2022Article
- Chemotherapy induces canalization of cell state in childhood B-cell precursor acute lymphoblastic leukemia.Nature cancer · 2021Article
- Developing New Agents for Treatment of Childhood Cancer: Challenges and Opportunities for Preclinical Testing.Journal of clinical medicine · 2021Article
- Hypoxia favors chemoresistance in T-ALL through an HIF1α-mediated mTORC1 inhibition loop.Blood advances · 2021Article
- Overcoming Glucocorticoid Resistance in Acute Lymphoblastic Leukemia: Repurposed Drugs Can Improve the Protocol.Frontiers in oncology · 2021Review
- Constitutive Activation of RAS/MAPK Pathway Cooperates with Trisomy 21 and Is Therapeutically Exploitable in Down Syndrome B-cell Leukemia.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020Article
- Challenges and Opportunities for Childhood Cancer Drug Development.Pharmacological reviews · 2019Review
- Article
- Metabolic reprogramming of acute lymphoblastic leukemia cells in response to glucocorticoid treatment.Cell death & disease · 2018Article
- Altered membrane rigidity via enhanced endogenous cholesterol synthesis drives cancer cell resistance to destruxins.Oncotarget · 2018Article
- Immunoregulation by IL-7R-targeting antibody-drug conjugates: overcoming steroid-resistance in cancer and autoimmune disease.Scientific reports · 2017Article
- Drug-induced amino acid deprivation as strategy for cancer therapy.Journal of hematology & oncology · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Relapse and acquired drug resistance in T-cell acute lymphoblastic leukemia (T-ALL) remains a significant clinical problem. This study was designed to establish a preclinical model of resistance to induction therapy in childhood T-ALL to examine the emergence of drug resistance and identify novel therapies. Patient-derived T-ALL xenografts in immune-deficient (non-obese diabetic/severe combined immunodeficient) mice were exposed to a four-drug combination of vincristine, dexamethasone (DEX), L-asparaginase and daunorubicin (VXLD). 'Relapse' xenografts were characterized by responses to drugs, changes in gene expression profiles and Connectivity Map (CMap) prediction of strategies to reverse drug resistance. Two of four xenografts developed ex vivo and in vivo drug resistance. Both resistant lines showed altered lipid and cholesterol metabolism, yet they had a distinct drug resistance pattern. CMap analyses reinforced these features, identifying the cholesterol pathway inhibitor simvastatin (SVT) as a potential therapy to overcome resistance. Combined ex vivo with DEX, SVT was significantly synergistic, yet when administered in vivo with VXLD it did not delay leukemia progression. Synergy of SVT with established chemotherapy may depend on higher drug doses than are tolerable in this model. Taken together, we have developed a clinically relevant in vivo model of T-ALL suitable to examine the emergence of drug resistance and to identify novel therapies.
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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.