ArticleHaematologica2012
The significance of PTEN and AKT aberrations in pediatric T-cell acute lymphoblastic leukemia.
Article in Haematologica, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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Who cites it
79 citing papers in PubMed, 125 citations in OpenAlex.
- Pediatric T-cell lymphoblastic leukemia evolves into relapse by clonal selection, acquisition of mutations and promoter hypomethylation.Haematologica · 2015Trial
- Trial
- PTEN-loss confers dependence on the guanylate synthesis enzyme IMPDH in T-cell acute lymphoblastic leukemia.EMBO molecular medicine · 2026Article
- PTEN-loss confers dependence on the guanylate synthesis enzyme IMPDH in T-cell acute lymphoblastic leukemia.bioRxiv : the preprint server for biology · 2025Article
- USP7 mutations are associated with adverse outcomes in pediatric T cell acute lymphoblastic leukemia and lymphoma.Annals of hematology · 2025Article
- T-cell acute lymphoblastic leukaemia: subtype prevalence, clinical outcome, and emerging targeted treatments.Leukemia · 2025Review
- Somatic mtDNA mutation burden shapes metabolic plasticity in leukemogenesis.Science advances · 2025Article
- Contribution of copy number to improve risk stratification of adult T-cell acute lymphoblastic leukemia patients enrolled in measurable residual disease-oriented trials.Haematologica · 2025Article
- SIL-TAL1-Positive Adult T-ALL with t(11;14)(p15;q11.2): A Rare Case Report Highlighting Prognostic Challenges and Treatment Implications.Journal of inflammation research · 2025Article
- Article
- ATM-deficient murine thymic T-cell lymphoblastic lymphomas are PTEN-deficient and require AKT signaling for survival.PloS one · 2024Article
- Resistance mechanism to Notch inhibition and combination therapy in human T-cell acute lymphoblastic leukemia.Blood advances · 2023Article
- Single-cell RNA sequencing distinctly characterizes the wide heterogeneity in pediatric mixed phenotype acute leukemia.Genome medicine · 2023Article
- Article
- TAL1 cooperates with PI3K/AKT pathway activation in T-cell acute lymphoblastic leukemia.Haematologica · 2022Article
- Novel Targeted Therapies for T-Cell Malignancies.Cancers · 2022Article
- Ectopic expression of a combination of 5 genes detects high risk forms of T-cell acute lymphoblastic leukemia.BMC genomics · 2022Article
- Either IL-7 activation of JAK-STAT or BEZ inhibition of PI3K-AKT-mTOR pathways dominates the single-cell phosphosignature ofHaematologica · 2022Article
- PTEN/PI3K/Akt pathway alters sensitivity of T-cell acute lymphoblastic leukemia to L-asparaginase.Scientific reports · 2022Article
- Article
19 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 8 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPI3K/AKT pathway mutations are found in T-cell acute lymphoblastic leukemia, but their overall impact and associations with other genetic aberrations is unknown. PTEN mutations have been proposed as secondary mutations that follow NOTCH1-activating mutations and cause cellular resistance to γ-secretase inhibitors. DESIGN AND
methodsThe impact of PTEN, PI3K and AKT aberrations was studied in a genetically well-characterized pediatric T-cell leukemia patient cohort (n=146) treated on DCOG or COALL protocols.
resultsPTEN and AKT E17K aberrations were detected in 13% and 2% of patients, respectively. Defective PTEN-splicing was identified in incidental cases. Patients without PTEN protein but lacking exon-, splice-, promoter mutations or promoter hypermethylation were present. PTEN/AKT mutations were especially abundant in TAL- or LMO-rearranged leukemia but nearly absent in TLX3-rearranged patients (P=0.03), the opposite to that observed for NOTCH1-activating mutations. Most PTEN/AKT mutant patients either lacked NOTCH1-activating mutations (P=0.006) or had weak NOTCH1-activating mutations (P=0.011), and consequently expressed low intracellular NOTCH1, cMYC and MUSASHI levels. T-cell leukemia patients without PTEN/AKT and NOTCH1-activating mutations fared well, with a cumulative incidence of relapse of only 8% versus 35% for PTEN/AKT and/or NOTCH1-activated patients (P=0.005).
conclusionsPI3K/AKT pathway aberrations are present in 18% of pediatric T-cell acute lymphoblastic leukemia patients. Absence of strong NOTCH1-activating mutations in these cases may explain cellular insensitivity to γ-secretase inhibitors.
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