The BH3-only protein NOXA is essential for apoptosis induction by BH3-mimetics targeting BCL2 or BCL-X in DLBCL.
1/5 보강
BCL2 inhibitors (BCL2i) have transformed the management of chronic lymphocytic leukaemia (CLL), but their use in more aggressive B-cell malignancies such as diffuse large B-Cell lymphoma (DLBCL) is co
APA
Yildirim N, Anders M, et al. (2026). The BH3-only protein NOXA is essential for apoptosis induction by BH3-mimetics targeting BCL2 or BCL-X in DLBCL.. British journal of haematology, 208(1), 96-105. https://doi.org/10.1111/bjh.70192
MLA
Yildirim N, et al.. "The BH3-only protein NOXA is essential for apoptosis induction by BH3-mimetics targeting BCL2 or BCL-X in DLBCL.." British journal of haematology, vol. 208, no. 1, 2026, pp. 96-105.
PMID
41047548 ↗
Abstract 한글 요약
BCL2 inhibitors (BCL2i) have transformed the management of chronic lymphocytic leukaemia (CLL), but their use in more aggressive B-cell malignancies such as diffuse large B-Cell lymphoma (DLBCL) is complicated by the more heterogeneous nature of the disease. Successful responses are limited to a subset of patients, highlighting the need for robust biomarkers predicting sensitivity. Here, we investigated the underlying mechanisms of inherent resistance to the BCL2i ABT-199 and BCL-X inhibitor A1331852, focusing on the roles of the principal pro-apoptotic BH3-only proteins NOXA and BIM. We show that NOXA deletion, but not BIM deletion, in BCL2 and BCL-X-dependent DLBCL cells both in vitro and in vivo resulted in a highly significant enhanced resistance to both BCL2i and BCL-X inhibitors. In contrast, NOXA deletion did not result in alteration of sensitivity to MCL1 inhibitors. NOXA loss was associated with increased stability and binding capacity of MCL1; binding of BIM to MCL1 was associated with resistance to ABT-199. Resistance to BCL2i and BCL-X inhibitors was abrogated by suppression of MCL1 expression. In conclusion, we show that NOXA is essential for the effectiveness of BH3-mimetics targeting BCL2/BCL-X; in the absence of NOXA, BIM displaced from BCL2/BCL-X can be bound by MCL1.
🏷️ 키워드 / MeSH 📖 같은 키워드 OA만
- Lymphoma
- Large B-Cell
- Diffuse
- Humans
- Proto-Oncogene Proteins c-bcl-2
- bcl-X Protein
- Apoptosis
- Sulfonamides
- Bridged Bicyclo Compounds
- Heterocyclic
- Animals
- Mice
- Cell Line
- Tumor
- Bcl-2-Like Protein 11
- Drug Resistance
- Neoplasm
- Antineoplastic Agents
- Peptide Fragments
- Proto-Oncogene Proteins
- Apoptosis Regulatory Proteins
- Isoquinolines
- Benzothiazoles
- BCL2 proteins
… 외 4개
🏷️ 같은 키워드 · 무료전문 — 이 논문 MeSH/keyword 기반
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