ArticleHaematologica2016
RNA sequencing unravels the genetics of refractory/relapsed T-cell acute lymphoblastic leukemia. Prognostic and therapeutic implications.
Article in Haematologica, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 48 citations in OpenAlex.
- Trial
- The DHODH inhibitor teriflunomide impedes cell proliferation and enhances chemosensitivity to daunorubicin (DNR) in T-cell acute lymphoblastic leukemia.Annals of hematology · 2024Article
- Decoding the genetic symphony: Profiling protein-coding and long noncoding RNA expression in T-acute lymphoblastic leukemia for clinical insights.PNAS nexus · 2024Article
- Integration of Genomic Sequencing Drives Therapeutic Targeting of PDGFRA in T-Cell Acute Lymphoblastic Leukemia/Lymphoblastic Lymphoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Pdx1 expression in hematopoietic cells activatesLeukemia & lymphoma · 2023Article
- Pediatric T-ALL type-1 and type-2 relapses develop along distinct pathways of clonal evolution.Leukemia · 2022Article
- Overcoming Steroid Resistance in Pediatric Acute Lymphoblastic Leukemia-The State-of-the-Art Knowledge and Future Prospects.International journal of molecular sciences · 2022Review
- Integrated genomic analyses identify high-risk factors and actionable targets in T-cell acute lymphoblastic leukemia.Blood science (Baltimore, Md.) · 2022Article
- MAPK-ERK is a central pathway in T-cell acute lymphoblastic leukemia that drives steroid resistance.Leukemia · 2021Article
- The Emerging Role of Suppressors of Cytokine Signaling (SOCS) in the Development and Progression of Leukemia.Cancers · 2021Review
- Review
- [Prognostic analysis of patients with mutations in the JAK/STAT signaling pathway in adult acute lymphoblastic leukemia].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2021Article
- CXCR4 allows T cell acute lymphoblastic leukemia to escape from JAK1/2 and BCL2 inhibition through CNS infiltration.Leukemia & lymphoma · 2021Article
- [The role and research progress of NOTCH1 in T-cell acute lymphoblastic leukemia].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2021Article
- Article
- A Nomogram for the Prediction of Progression and Overall Survival in Childhood Acute Lymphoblastic Leukemia.Frontiers in oncology · 2020Article
- The Key Roles of PTEN in T-Cell Acute Lymphoblastic Leukemia Development, Progression, and Therapeutic Response.Cancers · 2019Review
- Comprehensive long non-coding RNA expression profiling by RNA sequencing reveals potential biomarkers for acute myeloid leukemia risk.Cancer biomarkers : section A of Disease markers · 2019Article
- Differential Co-expression and Regulatory Network Analysis Uncover the Relapse Factor and Mechanism of T Cell Acute Leukemia.Molecular therapy. Nucleic acids · 2018Article
- Biological Aspects of mTOR in Leukemia.International journal of molecular sciences · 2018Review
Corrections and comments
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Authors and funding
22 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite therapeutic improvements, a sizable number of patients with T-cell acute lymphoblastic leukemia still have a poor outcome. To unravel the genomic background associated with refractoriness, we evaluated the transcriptome of 19 cases of refractory/early relapsed T-cell acute lymphoblastic leukemia (discovery cohort) by performing RNA-sequencing on diagnostic material. The incidence and prognostic impact of the most frequently mutated pathways were validated by Sanger sequencing on genomic DNA from diagnostic samples of an independent cohort of 49 cases (validation cohort), including refractory, relapsed and responsive cases. Combined gene expression and fusion transcript analyses in the discovery cohort revealed the presence of known oncogenes and identified novel rearrangements inducing overexpression, as well as inactivation of tumor suppressor genes. Mutation analysis identified JAK/STAT and RAS/PTEN as the most commonly disrupted pathways in patients with chemorefractory disease or early relapse, frequently in association with NOTCH1/FBXW7 mutations. The analysis on the validation cohort documented a significantly higher risk of relapse, inferior overall survival, disease-free survival and event-free survival in patients with JAK/STAT or RAS/PTEN alterations. Conversely, a significantly better survival was observed in patients harboring only NOTCH1/FBXW7 mutations: this favorable prognostic effect was abrogated by the presence of concomitant mutations. Preliminary in vitro assays on primary cells demonstrated sensitivity to specific inhibitors. These data document the negative prognostic impact of JAK/STAT and RAS/PTEN mutations in T-cell acute lymphoblastic leukemia and suggest the potential clinical application of JAK and PI3K/mTOR inhibitors in patients harboring mutations in these pathways.
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