ArticleLeukemia2018
Mutant JAK3 phosphoproteomic profiling predicts synergism between JAK3 inhibitors and MEK/BCL2 inhibitors for the treatment of T-cell acute lymphoblastic leukemia.
Article in Leukemia, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 48 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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
48 citing papers in PubMed, 1 synthesis or guideline pooled it, 87 citations in OpenAlex.
- The role of chemokines and interleukins in acute lymphoblastic leukemia: a systematic review.Journal of applied biomedicine · 2024Pooled it
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- Differential expression of cancer-related genes supports prediction of poor response to first-line treatments in T-ALL pediatric patients with high minimal residual disease.Molecular oncology · 2026Article
- Mining public mass spectrometry data to map the bull sperm membrane-associated proteome.Reproduction & fertility · 2026Article
- Promising Drugs Targeting Specific Mechanisms of Deregulation in T Cell Lineage Acute Lymphoblastic Leukemia.Oncology and therapy · 2025Review
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- Glucocorticoid Therapy in Acute Lymphoblastic Leukemia: Navigating Short-Term and Long-Term Effects and Optimal Regimen Selection.Current hematologic malignancy reports · 2024Review
- Janus Kinase 3 (JAK3): A Critical Conserved Node in Immunity Disrupted in Immune Cell Cancer and Immunodeficiency.International journal of molecular sciences · 2024Review
- PI3K/mTOR is a therapeutically targetable genetic dependency in diffuse intrinsic pontine glioma.The Journal of clinical investigation · 2024Article
- Prognostic impact ofTherapeutic advances in hematology · 2024Article
- Targeted therapy and immunotherapy for T cell acute lymphoblastic leukemia/lymphoma.Annals of hematology · 2023Review
- Exploring the Apoptotic-Induced Biochemical Mechanism of Traditional Thai Herb (Kerra™) Extract in HCT116 Cells Using a Label-Free Proteomics Approach.Medicina (Kaunas, Lithuania) · 2023Article
- ONC201 in Combination with Paxalisib for the Treatment of H3K27-Altered Diffuse Midline Glioma.Cancer research · 2023Article
- Notch Partners in the Long Journey of T-ALL Pathogenesis.International journal of molecular sciences · 2023Review
- Phospho-heavy-labeled-spiketide FAIMS stepped-CV DDA (pHASED) provides real-time phosphoproteomics data to aid in cancer drug selection.Clinical proteomics · 2022Article
- Somatic Mutations Alter Interleukin Signaling Pathways in Grade II Invasive Breast Cancer Patients: An Egyptian Experience.Current issues in molecular biology · 2022Article
- A multiparametric niche-like drug screening platform in acute myeloid leukemia.Blood cancer journal · 2022Article
- Quantitative proteomic dataset of mouse caput epididymal epithelial cells exposed to acrylamideData in brief · 2022Article
- JAK3 mutations and mitochondrial apoptosis resistance in T-cell acute lymphoblastic leukemia.Leukemia · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations in the interleukin-7 receptor (IL7R) or the Janus kinase 3 (JAK3) kinase occur frequently in T-cell acute lymphoblastic leukemia (T-ALL) and both are able to drive cellular transformation and the development of T-ALL in mouse models. However, the signal transduction pathways downstream of JAK3 mutations remain poorly characterized. Here we describe the phosphoproteome downstream of the JAK3(L857Q)/(M511I) activating mutations in transformed Ba/F3 lymphocyte cells. Signaling pathways regulated by JAK3 mutants were assessed following acute inhibition of JAK1/JAK3 using the JAK kinase inhibitors ruxolitinib or tofacitinib. Comprehensive network interrogation using the phosphoproteomic signatures identified significant changes in pathways regulating cell cycle, translation initiation, mitogen-activated protein kinase and phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/AKT signaling, RNA metabolism, as well as epigenetic and apoptotic processes. Key regulatory proteins within pathways that showed altered phosphorylation following JAK inhibition were targeted using selumetinib and trametinib (MEK), buparlisib (PI3K) and ABT-199 (BCL2), and found to be synergistic in combination with JAK kinase inhibitors in primary T-ALL samples harboring JAK3 mutations. These data provide the first detailed molecular characterization of the downstream signaling pathways regulated by JAK3 mutations and provide further understanding into the oncogenic processes regulated by constitutive kinase activation aiding in the development of improved combinatorial treatment regimens.
Identifiers
What OpenQuestion holds
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.