Relative mitochondrial priming of myeloblasts and normal HSCs determines chemotherapeutic success in AML.
Relative mitochondrial priming of myeloblasts and normal HSCs determines chemotherapeutic success in AML.
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DOI：
10.1016/j.cell.2012.08.038
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发表时间：
2012-10-12
期刊：
影响因子：
64.5
通讯作者：
Letai A
中科院分区：
文献类型：
--
作者：
Vo TT;Ryan J;Carrasco R;Neuberg D;Rossi DJ;Stone RM;Deangelo DJ;Frattini MG;Letai A
Despite decades of successful use of cytotoxic chemotherapy in acute myelogenous leukemia (AML), the biological basis for its differential success among individuals and for the existence of a therapeutic index has remained obscure. Rather than taking a genetic approach favored by many, we took a functional approach to ask how differential mitochondrial readiness for apoptosis (“priming”) might explain individual variation in clinical behavior. We found that mitochondrial priming measured by BH3 profiling was a determinant of initial response to induction chemotherapy, relapse following remission, and requirement for allogeneic bone marrow transplantation. Differential priming between malignant myeloblasts and normal hematopoietic stem cells supports a mitochondrial basis to the therapeutic index for chemotherapy. BH3 profiling identified BCL-2 inhibition as a targeted strategy likely to have a useful therapeutic index. BH3 profiling refines predictive information provided by conventional biomarkers currently in use, and thus may itself have utility as a clinical predictive biomarker.
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DOI：
10.1038/nrc2607
发表时间：
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期刊：
Nature reviews. Cancer
影响因子：
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通讯作者：
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16
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