ArticleHaematologica2019
Autophagy inhibition as a potential future targeted therapy for ETV6-RUNX1-driven B-cell precursor acute lymphoblastic leukemia.
Article in Haematologica, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 55 citations in OpenAlex.
- ETV6 Rearrangement Suppresses CDKN1B Transcription by Disrupting an Intragenic Super-enhancer in Acute Lymphoblastic Leukemia.Cancer research · 2026Article
- Advances in targeted therapies for pediatric tumors.Acta pharmacologica Sinica · 2026Article
- Pharmacological Modulation of Autophagy Can Sensitize Acute Lymphoblastic Leukemia Cell Lines to Dexamethasone.Cancers · 2026Article
- Relapse in childhood B-cell precursor acute lymphoblastic leukemia: insights from transcriptomic signatures of diagnostic bone marrow.Frontiers in oncology · 2026Review
- Identification and validation of prognostic genes associated with m6A-regulated programmed cell death in acute lymphoblastic leukemia.Scientific reports · 2025Article
- H1-0 is a specific mediator of the repressive ETV6::RUNX1 transcriptional landscape in preleukemia and B cell acute lymphoblastic leukemia.HemaSphere · 2025Article
- Cyclin C promotes development and progression of B-cell acute lymphoblastic leukemia by counteracting p53-mediated stress responses.Haematologica · 2025Article
- Crosstalk Between Autophagy and Oxidative Stress in Hematological Malignancies: Mechanisms, Implications, and Therapeutic Potential.Antioxidants (Basel, Switzerland) · 2025Review
- Integrating bulk RNA-seq and scRNA-seq data to explore diverse cell death patterns and develop a programmed cell death-related relapse prediction model in pediatric B-ALL.Scientific reports · 2025Article
- Autophagy-related 7 (ATG7) regulates food intake and liver health during asparaginase exposure.The Journal of biological chemistry · 2025Article
- Article
- Proteogenomic profiling uncovers differential therapeutic vulnerabilities betweenHaematologica · 2024Article
- The potential role of RNA sequencing in diagnosing unexplained insensitivity to conventional chemotherapy in pediatric patients with B-cell acute lymphoblastic leukemia.BMC medical genomics · 2024Article
- Targeting autophagy as a therapeutic strategy in pediatric acute lymphoblastic leukemia.Scientific reports · 2024Article
- The Diverse Roles of ETV6 Alterations in B-Lymphoblastic Leukemia and Other Hematopoietic Cancers.Advances in experimental medicine and biology · 2024Review
- Review
- Review
- ETV6 Deficiency Unlocks ERG-Dependent Microsatellite Enhancers to Drive Aberrant Gene Activation in B-Lymphoblastic Leukemia.Blood cancer discovery · 2023Article
- Integrating copy number data of 64 iAMP21 BCP-ALL patients narrows the common region of amplification to 1.57 Mb.Frontiers in oncology · 2023Article
- Possible mechanism of metabolic and drug resistance with L-asparaginase therapy in childhood leukaemia.Frontiers in oncology · 2023Review
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Translocation t(12;21), resulting in the ETV6-RUNX1 (or TEL-AML1) fusion protein, is present in 25% of pediatric patients with B-cell precursor acute lymphoblastic leukemia and is considered a first hit in leukemogenesis. A targeted therapy approach is not available for children with this subtype of leukemia. To identify the molecular mechanisms underlying ETV6-RUNX1-driven leukemia, we performed gene expression profiling of healthy hematopoietic progenitors in which we ectopically expressed ETV6-RUNX1. We reveal an ETV6-RUNX1-driven transcriptional network that induces proliferation, survival and cellular homeostasis. In addition, Vps34, an important regulator of autophagy, was found to be induced by ETV6-RUNX1 and up-regulated in ETV6-RUNX1-positive leukemic patient cells. We show that induction of Vps34 was transcriptionally regulated by ETV6-RUNX1 and correlated with high levels of autophagy. Knockdown of Vps34 in ETV6-RUNX1-positive cell lines severely reduced proliferation and survival. Inhibition of autophagy by hydroxychloroquine, a well-tolerated autophagy inhibitor, reduced cell viability in both ETV6-RUNX1-positive cell lines and primary acute lymphoblastic leukemia samples, and selectively sensitized primary ETV6-RUNX1-positive leukemia samples to L asparaginase. These findings reveal a causal relationship between ETV6-RUNX1 and autophagy, and provide pre-clinical evidence for the efficacy of autophagy inhibitors in ETV6-RUNX1-driven leukemia.
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