ArticleCellular and molecular life sciences : CMLS2021
Targeted inhibition of eIF4A suppresses B-cell receptor-induced translation and expression of MYC and MCL1 in chronic lymphocytic leukemia cells.
Article in Cellular and molecular life sciences : CMLS, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 35 citations in OpenAlex.
- PDCD4: A critical regulator in leukemic signaling networks and its therapeutic potential.Molecular biology reports · 2025Review
- Role of DEAD/DEAH-box helicases in immunity, infection and cancers.Cell communication and signaling : CCS · 2025Review
- A Csde1-Strap complex regulates plasma cell differentiation by coupling mRNA translation and decay.Nature communications · 2025Article
- Rocaglamide Suppresses Allergic Reactions by Regulating IL-4 Receptor Signaling.Molecules (Basel, Switzerland) · 2025Article
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- Critical and differential roles of eIF4A1 and eIF4A2 in B-cell development and function.Cellular & molecular immunology · 2025Article
- RBM47 promotes cell proliferation and immune evasion by upregulating PDIA6: a novel mechanism of pancreatic cancer progression.Journal of translational medicine · 2024Article
- DMDA-PatA mediates RNA sequence-selective translation repression by anchoring eIF4A and DDX3 to GNG motifs.Nature communications · 2024Article
- Bioactive nutraceuticals as G4 stabilizers: potential cancer prevention and therapy-a critical review.Naunyn-Schmiedeberg's archives of pharmacology · 2024Review
- RNA helicase EIF4A1-mediated translation is essential for the GC response.Life science alliance · 2024Article
- Power out chronic lymphocytic leukemia: unplugging OXPHOS/mTOR pathways to overcome venetoclax resistance.Haematologica · 2024Article
- Electron transport chain and mTOR inhibition synergistically decrease CD40 signaling and counteract venetoclax resistance in chronic lymphocytic leukemia.Haematologica · 2024Article
- mTORC1-selective activation of translation elongation promotes disease progression in chronic lymphocytic leukemia.Leukemia · 2023Article
- Targeting mRNA translation aberrations: A novel approach for therapy in chronic lymphocytic leukemia.Cancer communications (London, England) · 2023Article
- Cardiac glycoside ouabain efficiently targets leukemic stem cell apoptotic machinery independent of cell differentiation status.Cell communication and signaling : CCS · 2023Article
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- Novel eIF4A1 inhibitors with anti-tumor activity in lymphoma.Molecular medicine (Cambridge, Mass.) · 2022Article
- Allergen protease-activated stress granule assembly and gasdermin D fragmentation control interleukin-33 secretion.Nature immunology · 2022Article
- B-cell receptor signaling induces proteasomal degradation of PDCD4 via MEK1/2 and mTORC1 in malignant B cells.Cellular signalling · 2022Article
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Signaling via the B-cell receptor (BCR) is a key driver and therapeutic target in chronic lymphocytic leukemia (CLL). BCR stimulation of CLL cells induces expression of eIF4A, an initiation factor important for translation of multiple oncoproteins, and reduces expression of PDCD4, a natural inhibitor of eIF4A, suggesting that eIF4A may be a critical nexus controlling protein expression downstream of the BCR in these cells. We, therefore, investigated the effect of eIF4A inhibitors (eIF4Ai) on BCR-induced responses. We demonstrated that eIF4Ai (silvestrol and rocaglamide A) reduced anti-IgM-induced global mRNA translation in CLL cells and also inhibited accumulation of MYC and MCL1, key drivers of proliferation and survival, respectively, without effects on upstream signaling responses (ERK1/2 and AKT phosphorylation). Analysis of normal naïve and non-switched memory B cells, likely counterparts of the two main subsets of CLL, demonstrated that basal RNA translation was higher in memory B cells, but was similarly increased and susceptible to eIF4Ai-mediated inhibition in both. We probed the fate of MYC mRNA in eIF4Ai-treated CLL cells and found that eIF4Ai caused a profound accumulation of MYC mRNA in anti-IgM treated cells. This was mediated by MYC mRNA stabilization and was not observed for MCL1 mRNA. Following drug wash-out, MYC mRNA levels declined but without substantial MYC protein accumulation, indicating that stabilized MYC mRNA remained blocked from translation. In conclusion, BCR-induced regulation of eIF4A may be a critical signal-dependent nexus for therapeutic attack in CLL and other B-cell malignancies, especially those dependent on MYC and/or MCL1.
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