ArticleOncotarget2015
RPPA-based protein profiling reveals eIF4G overexpression and 4E-BP1 serine 65 phosphorylation as molecular events that correspond with a pro-survival phenotype in chronic lymphocytic leukemia.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 21 citations in OpenAlex.
- Unraveling the impact of chemoradiotherapy on hematopoietic function in cancer patients: a metabolomics-driven mechanistic investigation.Molecular and cellular biochemistry · 2026Review
- Review
- Targeting eIF4F translation initiation complex with SBI-756 sensitises B lymphoma cells to venetoclax.British journal of cancer · 2021Article
- Dual Inhibition of mTORC1/2 Reduces Migration of Cholangiocarcinoma Cells by Regulation of Matrixmetalloproteinases.Frontiers in cell and developmental biology · 2021Article
- Developing the novel bioinformatics algorithms to systematically investigate the connections among survival time, key genes and proteins for Glioblastoma multiforme.BMC bioinformatics · 2020Article
- A dual PI3 kinase/mTOR inhibitor BEZ235 reverses doxorubicin resistance in ABCB1 overexpressing ovarian and pancreatic cancer cell lines.Biochimica et biophysica acta. General subjects · 2020Article
- Paip1 overexpression is involved in the progression of gastric cancer and predicts shorter survival of diagnosed patients.OncoTargets and therapy · 2019Article
- hsa‑miR‑24 suppresses metastasis in nasopharyngeal carcinoma by regulating the c‑Myc/epithelial‑mesenchymal transition axis.Oncology reports · 2018Article
- Proteomics profiling identifies induction of caveolin-1 in chronic lymphocytic leukemia cells by bone marrow stromal cells.Leukemia & lymphoma · 2018Article
- PI3Kδ-selective and PI3Kα/δ-combinatorial inhibitors in clinical development for B-cell non-Hodgkin lymphoma.Expert opinion on investigational drugs · 2017Review
- The PI3K/mTOR dual inhibitor BEZ235 suppresses proliferation and migration and reverses multidrug resistance in acute myeloid leukemia.Acta pharmacologica Sinica · 2017Article
- Integrated Strategies to Gain a Systems-Level View of Dynamic Signaling Networks.Methods in enzymology · 2017Article
- Review
- 4E-BP1, a multifactor regulated multifunctional protein.Cell cycle (Georgetown, Tex.) · 2016Review
- Pharmacological targeting of PI3K isoforms as a therapeutic strategy in chronic lymphocytic leukaemia.Leukemia research reports · 2015Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
Chronic lymphocytic leukemia (CLL), the most common adult leukemia, remains incurable despite advancements in treatment regimens over the past decade. Several expression profile studies have been pursued to better understand CLL pathogenesis. However, these large-scale studies only provide information at the transcriptional level. To better comprehend the differential protein changes that take place in CLL, we performed a reverse-phase protein array (RPPA) analysis using 167 different antibodies on B-cell lysates from 18 CLL patients and 6 normal donors. From our analysis, we discovered an enrichment of protein alterations involved with mRNA translation, specifically upregulation of the translation initiator eIF4G and phosphorylation of the cap-dependent translation inhibitor 4E-BP1 at serine 65. Interestingly, 4E-BP1 phosphorylation occurred independently of AKT phosphorylation, suggesting a disconnect between PI3K/AKT pathway activation and 4E-BP1 phosphorylation. Based on these results, we treated primary CLL samples with NVP-BEZ235, a PI3K/mTOR dual inhibitor, and compared its apoptotic-inducing potential against the BTK inhibitor Ibrutinib and the PI3Kδ inhibitor Idelalisib. We demonstrated that treatment with NVP-BEZ235 caused greater apoptosis, greater apoptotic cleavage of eIF4G, and greater dephosphorylation of 4E-BP1 in primary CLL cells. Taken together, these results highlight the potential dependence of eIF4G overexpression and 4E-BP1 phosphorylation in CLL survival.
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