Venetoclax inhibits autophagy in chronic lymphocytic leukemia cells
Venetoclax (VCX) is a BCL2 inhibitor approved for treating B cell-derived leukemia, including chronic lymphocytic leukemia (CLL). VCX’s role in apoptosis induction is well-defined, whereas its other mechanistic roles need to be clarified. Autophagy is an intracellular degradation process involving t...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | Autophagy Reports |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/27694127.2023.2169518 |
| _version_ | 1797685733536825344 |
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| author | Yongqiang Chen Sara E. F. Kost Xiaoyan Yang Versha Banerji James B. Johnston Sachin Katyal Spencer B. Gibson |
| author_facet | Yongqiang Chen Sara E. F. Kost Xiaoyan Yang Versha Banerji James B. Johnston Sachin Katyal Spencer B. Gibson |
| author_sort | Yongqiang Chen |
| collection | DOAJ |
| description | Venetoclax (VCX) is a BCL2 inhibitor approved for treating B cell-derived leukemia, including chronic lymphocytic leukemia (CLL). VCX’s role in apoptosis induction is well-defined, whereas its other mechanistic roles need to be clarified. Autophagy is an intracellular degradation process involving the lysosome, playing a fundamental role in cancer cell survival and death. In this study, we aim to investigate VCX’s function in autophagy. Following the measurement of autophagic flux by western blot and fluorescent microscopy, we demonstrate that VCX is a novel autophagy inhibitor and reduces the level of the essential autophagy pathway protein ATG12 (autophagy-related 12). VCX sensitizes B cell lines and primary CLL cells to cell death induced by amino acid starvation or ibrutinib. These findings provide a rationale for VCX treatment in combination therapies that inhibit the pro-cell survival function of autophagy in B cell-derived malignancies. Abbreviations: ATG12, autophagy-related 12; BCL2, BCL2 apoptosis regulator; CLL, chronic lymphocytic leukemia; CQ, chloroquine; IBR, ibrutinib; BTK, Bruton’s tyrosine kinase; LC3B, MAP1LC3B (microtubule-associated protein 1 light chain 3 beta); VCX, venetoclax; BECN1, beclin 1 |
| first_indexed | 2024-03-12T00:55:36Z |
| format | Article |
| id | doaj.art-d368c74e59604da4b9c7a7efa9b15608 |
| institution | Directory Open Access Journal |
| issn | 2769-4127 |
| language | English |
| last_indexed | 2024-03-12T00:55:36Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Autophagy Reports |
| spelling | doaj.art-d368c74e59604da4b9c7a7efa9b156082023-09-14T13:24:40ZengTaylor & Francis GroupAutophagy Reports2769-41272023-12-012110.1080/27694127.2023.21695182169518Venetoclax inhibits autophagy in chronic lymphocytic leukemia cellsYongqiang ChenSara E. F. KostXiaoyan Yang0Versha BanerjiJames B. JohnstonSachin KatyalSpencer B. GibsonUniversity of AlbertaVenetoclax (VCX) is a BCL2 inhibitor approved for treating B cell-derived leukemia, including chronic lymphocytic leukemia (CLL). VCX’s role in apoptosis induction is well-defined, whereas its other mechanistic roles need to be clarified. Autophagy is an intracellular degradation process involving the lysosome, playing a fundamental role in cancer cell survival and death. In this study, we aim to investigate VCX’s function in autophagy. Following the measurement of autophagic flux by western blot and fluorescent microscopy, we demonstrate that VCX is a novel autophagy inhibitor and reduces the level of the essential autophagy pathway protein ATG12 (autophagy-related 12). VCX sensitizes B cell lines and primary CLL cells to cell death induced by amino acid starvation or ibrutinib. These findings provide a rationale for VCX treatment in combination therapies that inhibit the pro-cell survival function of autophagy in B cell-derived malignancies. Abbreviations: ATG12, autophagy-related 12; BCL2, BCL2 apoptosis regulator; CLL, chronic lymphocytic leukemia; CQ, chloroquine; IBR, ibrutinib; BTK, Bruton’s tyrosine kinase; LC3B, MAP1LC3B (microtubule-associated protein 1 light chain 3 beta); VCX, venetoclax; BECN1, beclin 1http://dx.doi.org/10.1080/27694127.2023.2169518apoptosisatg12autophagic fluxb cellsbcl2cell survivalchloroquine (cq)ibrutiniblc3clltargeted therapy |
| spellingShingle | Yongqiang Chen Sara E. F. Kost Xiaoyan Yang Versha Banerji James B. Johnston Sachin Katyal Spencer B. Gibson Venetoclax inhibits autophagy in chronic lymphocytic leukemia cells Autophagy Reports apoptosis atg12 autophagic flux b cells bcl2 cell survival chloroquine (cq) ibrutinib lc3 cll targeted therapy |
| title | Venetoclax inhibits autophagy in chronic lymphocytic leukemia cells |
| title_full | Venetoclax inhibits autophagy in chronic lymphocytic leukemia cells |
| title_fullStr | Venetoclax inhibits autophagy in chronic lymphocytic leukemia cells |
| title_full_unstemmed | Venetoclax inhibits autophagy in chronic lymphocytic leukemia cells |
| title_short | Venetoclax inhibits autophagy in chronic lymphocytic leukemia cells |
| title_sort | venetoclax inhibits autophagy in chronic lymphocytic leukemia cells |
| topic | apoptosis atg12 autophagic flux b cells bcl2 cell survival chloroquine (cq) ibrutinib lc3 cll targeted therapy |
| url | http://dx.doi.org/10.1080/27694127.2023.2169518 |
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