Ex Vivo Mitochondrial Respiration Parallels Biochemical Response to Ibrutinib in CLL Cells
| العنوان: | Ex Vivo Mitochondrial Respiration Parallels Biochemical Response to Ibrutinib in CLL Cells |
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| المؤلفون: | Spencer B. Gibson, Subir K. Roy Chowdhury, Cheryl Peltier, James B. Johnston, Aaron J. Marshall, Sen Hou, Versha Banerji, Amandeep Singh |
| المصدر: | Cancers Cancers, Vol 13, Iss 354, p 354 (2021) |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Cancer Research, Chemokine, plasma chemokine (C-C motif) ligands 3 and 4 (CCL3 and CCL4), Chronic lymphocytic leukemia, lactate dehydrogenase (LDH), lcsh:RC254-282, 03 medical and health sciences, chemistry.chemical_compound, B-cell receptor (BCR), 0302 clinical medicine, Lactate dehydrogenase, hemic and lymphatic diseases, mitochondrial respiration, Respiration, chronic lymphocytic leukemia (CLL), Bruton tyrosine kinase (BTK) inhibitor, medicine, Keywords: mitochondrial respiration, β-2 microglobulin (β-2 M), biology, Brief Report, breakpoint cluster region, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, 030104 developmental biology, Oncology, chemistry, Apoptosis, 030220 oncology & carcinogenesis, Ibrutinib, ibrutinib (IB), Cancer research, biology.protein, Ex vivo |
| الوصف: | Simple Summary Chronic lymphocytic leukemia (CLL) is a cancer that is characterized by dysfunctional mitochondria. This results in a deranged mitochondrial metabolism. Many drugs are tested using simple live or dead cell assays and as such the impact on the altered mitochondrial function is not evaluated. One such drug is ibrutinib. The use of ibrutinib at full doses can lead to significant side effects resulting in dose reduction or even discontinuation of the drug in clinical practice. In this study, we reviewed the effect of the dose of ibrutinib on mitochondrial function of the CLL cells from patients treated with ibrutinib and did not observe any difference in the mitochondrial respiration. We also evaluated the effect of progression of CLL cells from patients on ibrutinib treatment and the impact on mitochondrial respiration. We believe our findings are novel and suggest that evaluation of mitochondrial function of CLL cells is of importance to help design safe treatments in the preclinical setting. Abstract Mitochondrial respiration is becoming more commonly used as a preclinical tool and potential biomarker for chronic lymphocytic leukemia (CLL) and activated B-cell receptor (BCR) signaling. However, respiration parameters have not been evaluated with respect to dose of ibrutinib given in clinical practice or the effect of progression on ibrutinib treatment on respiration of CLL cells. We evaluated the impact of low and standard dose ibrutinib on CLL cells from patients treated in vivo on mitochondrial respiration using Oroboros oxygraph. Cytokines CCL3 and CCL4 were evaluated using the Mesoscale. Western blot analysis was used to evaluate the BCR and apoptotic pathways. We observed no difference in the mitochondrial respiration rates or levels of plasma chemokine (C-C motif) ligands 3 and 4 (CCL3/CCL4), β-2 microglobulin (β-2 M) and lactate dehydrogenase (LDH) between low and standard doses of ibrutinib. This may confirm why clinical observations of the safety and efficacy of low dose ibrutinib are observed in practice. Of interest, we also observed that the mitochondrial respiration of CLL cells paralleled the increase in β-2 M and LDH at progression. Our study further supports mitochondrial respiration as a biomarker for response and progression on ibrutinib in CLL cells and a valuable pre-clinical tool. |
| تدمد: | 2072-6694 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4d1580e7c111b69e856b2446d3c5c6fb https://pubmed.ncbi.nlm.nih.gov/33477957 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....4d1580e7c111b69e856b2446d3c5c6fb |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20726694 |
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