ArticleLeukemia2016
MEK and PI3K-AKT inhibitors synergistically block activated IL7 receptor signaling in T-cell acute lymphoblastic leukemia.
Article in Leukemia, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 90 citations in OpenAlex.
- Article
- Cytokines, Signaling and Epigenetic Mechanisms: Shaping the Acute Lymphoblastic Leukemia Microenvironment.Cells · 2026Review
- The Interleukin-7 Receptor Signaling Pathway and Its Perturbation in Immunodeficiency, Autoimmune Disease and Lymphoid Malignancy.Biomolecules · 2026Review
- High-Frequency Mutations in TP53, AXIN1, CTNNB1, and KRAS, and Polymorphisms in JAK1 Genes Among Mongolian HCC Patients.Cancer reports (Hoboken, N.J.) · 2025Article
- Clioquinol inhibits angiogenesis by promoting VEGFR2 degradation and synergizes with AKT inhibition to suppress triple-negative breast cancer vascularization.Angiogenesis · 2025Article
- IL-7 secreted by keratinocytes induces melanogenesis via c-kit/MAPK signaling pathway in Melan-a melanocytes.Archives of dermatological research · 2025Article
- Oncogenic and immunological targets for matched therapy of pediatric blood cancer patients: Dutch iTHER study experience.HemaSphere · 2024Article
- MAPK/ERK and PI3K/AKT signaling pathways are activated in adolescent and adult acute lymphoblastic leukemia.Cancer reports (Hoboken, N.J.) · 2023Article
- Circulating Biomarkers Associated with the Diagnosis and Prognosis of B-Cell Progenitor Acute Lymphoblastic Leukemia.Cancers · 2023Review
- Pediatric T-cell acute lymphoblastic leukemia blast signature and MRD associated immune environment changes defined by single cell transcriptomics analysis.Scientific reports · 2023Article
- Identification of NRF2 Activation as a Prognostic Biomarker in T-Cell Acute Lymphoblastic Leukaemia.International journal of molecular sciences · 2023Article
- Integrated multi-omics analyses reveal homology-directed repair pathway as a unique dependency in near-haploid leukemia.Blood cancer journal · 2023Article
- Review
- STAT5 does not drive steroid resistance in T-cell acute lymphoblastic leukemia despite the activation ofHaematologica · 2023Article
- Targeting Leukemia-Initiating Cells and Leukemic Niches: The Next Therapy Station for T-Cell Acute Lymphoblastic Leukemia?Cancers · 2022Review
- The Role of IL-7 and IL-7R in Cancer Pathophysiology and Immunotherapy.International journal of molecular sciences · 2022Review
- Interleukin-7 regulates CD127 expression and promotes CD8BMC immunology · 2022Article
- MEF2C opposes Notch in lymphoid lineage decision and drives leukemia in the thymus.JCI insight · 2022Article
- JAK3 mutations and mitochondrial apoptosis resistance in T-cell acute lymphoblastic leukemia.Leukemia · 2022Article
- Article
6 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We identified mutations in the IL7Ra gene or in genes encoding the downstream signaling molecules JAK1, JAK3, STAT5B, N-RAS, K-RAS, NF1, AKT and PTEN in 49% of patients with pediatric T-cell acute lymphoblastic leukemia (T-ALL). Strikingly, these mutations (except RAS/NF1) were mutually exclusive, suggesting that they each cause the aberrant activation of a common downstream target. Expressing these mutant signaling molecules-but not their wild-type counterparts-rendered Ba/F3 cells independent of IL3 by activating the RAS-MEK-ERK and PI3K-AKT pathways. Interestingly, cells expressing either IL7Ra or JAK mutants are sensitive to JAK inhibitors, but respond less robustly to inhibitors of the downstream RAS-MEK-ERK and PI3K-AKT-mTOR pathways, indicating that inhibiting only one downstream pathway is not sufficient. Here, we show that inhibiting both the MEK and PI3K-AKT pathways synergistically prevents the proliferation of BaF3 cells expressing mutant IL7Ra, JAK and RAS. Furthermore, combined inhibition of MEK and PI3K/AKT was cytotoxic to samples obtained from 6 out of 11 primary T-ALL patients, including 1 patient who had no mutations in the IL7R signaling pathway. Taken together, these results suggest that the potent cytotoxic effects of inhibiting both MEK and PI3K/AKT should be investigated further as a therapeutic option using leukemia xenograft models.
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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.