ArticleInternational journal of molecular sciences2019
Heterogeneous Pattern of Dependence on Anti-Apoptotic BCL-2 Family Proteins upon CHOP Treatment in Diffuse Large B-Cell Lymphoma.
Article in International journal of molecular sciences, 2019. 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.
- The BH3-only protein NOXA is essential for apoptosis induction by BH3-mimetics targeting BCL2 or BCL-XBritish journal of haematology · 2026Article
- KAT/3BP: A Metabolism-Targeting Agent with Single and Combination Activity in Aggressive B-Cell Lymphomas.Cancers · 2025Article
- HDAC10 and its implications in Sézary syndrome pathogenesis.Frontiers in cell and developmental biology · 2025Article
- Measles Virus-Based Genetic Modifications: Progress in Hematological Malignancy Treatment.OncoTargets and therapy · 2025Review
- Combination Treatment of Resistant Acute Promyelocytic Leukemia Cells with Arsenic Trioxide and Anti-Apoptotic Gene Inhibitors.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Targeting CD19-positive lymphomas with the antibodydrug conjugate loncastuximab tesirine: preclinical evidence of activity as a single agent and in combination therapy.Haematologica · 2024Article
- Article
- Navitoclax Most Promising BH3 Mimetic for Combination Therapy in Hodgkin Lymphoma.International journal of molecular sciences · 2022Article
- The mitochondrial anti-apoptotic dependencies of hematologic malignancies: from disease biology to advances in precision medicine.Haematologica · 2022Review
- A Novel Defined Super-Enhancer Associated Gene Signature to Predict Prognosis in Patients With Diffuse Large B-Cell Lymphoma.Frontiers in genetics · 2022Article
- Article
- MCL-1 dependency as a novel vulnerability for aggressive B cell lymphomas.Blood cancer journal · 2021Article
- Drug Resistance in Hematological Malignancies.International journal of molecular sciences · 2020Article
- BCL-2 family deregulation in colorectal cancer: potential for BH3 mimetics in therapy.Apoptosis : an international journal on programmed cell death · 2020Review
- Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Expression of the anti-apoptotic B-cell lymphoma 2 (BCL-2) protein in patients with diffuse large B-cell lymphoma (DLBCL) strongly correlates with resistance to standard therapy with cyclophosphamide, vincristine, doxorubicin, prednisolone, and rituximab (R-CHOP). Although studies focus mainly on the contribution of BCL-2, here we also investigate the contribution of other anti-apoptotic proteins to CHOP-therapy resistance in DLBCL. Functional dynamic BCL-2 homology (BH)3 profiling was applied to DLBCL cell lines upon CHOP treatment or single CHOP compounds. Cell-specific anti-apoptotic dependencies were validated with corresponding BH3-mimetics. We found high expression of anti-apoptotic BCL-2, MCL-1, and BCL-XL in DLBCL cell lines and patients. CHOP treatment resulted in both enhanced and altered anti-apoptotic dependency. Enhanced sensitivity to different BH3-mimetics after CHOP treatment was confirmed in specific cell lines, indicating heterogeneity of CHOP-induced resistance in DLBCL. Analysis of single CHOP compounds demonstrated that similar changes could also be induced by doxorubicin or vincristine, providing evidence for clinical combination therapies of doxorubicin or vincristine with BH3-mimetics in DLBCL. In conclusion, we show for the first time that CHOP treatment induces increased anti-apoptotic dependency on MCL-1 and BCL-XL, and not just BCL-2. These results provide new perspectives for the treatment of CHOP-resistant DLBCL and underline the potential of BH3 profiling in predicting therapy outcomes.
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