Synergy against PML-RARa: targeting transcription, proteolysis, differentiation, and self-renewal in acute promyelocytic leukemia.
Synergy against PML-RARa: targeting transcription, proteolysis, differentiation, and self-renewal in acute promyelocytic leukemia.
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DOI：
10.1084/jem.20131121
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发表时间：
2013-12-16
期刊：
影响因子：
--
通讯作者：
Pandolfi PP
中科院分区：
文献类型：
--
作者：
Dos Santos GA;Kats L;Pandolfi PP
Pandolfi等人对全反式维甲酸和三氧化二砷治疗之间的协同作用及其对急性早幼粒细胞白血病的作用机制进行了深入讨论。急性早幼粒细胞白血病（APL）是由嵌合癌蛋白驱动的血液恶性肿瘤，所述嵌合癌蛋白含有与最常见的早幼粒细胞白血病蛋白（PML）的N末端配偶体融合的视黄酸受体-a（RARa）的C末端。从机制上讲，PML-RAR α作为RAR α和非RAR α靶基因的转录阻遏物，并拮抗调节多种信号传导途径的PML核体的形成和功能。PML-RAR α相关APL对全反式维甲酸（ATRA）和三氧化二砷（ATO）敏感的经验发现，以及随后对这些药物作用机制的理解，已经导致人们努力了解分子事件对APL细胞分化、白血病起始细胞（LIC）清除和体外和体内疾病根除的贡献。重要的是，从这些研究中收集到的机制见解不仅使人们更好地了解APL本身，而且还为其他恶性肿瘤提供了宝贵的经验教训。
Pandolfi et al. provide an in-depth discussion on the synergism between all-trans-retinoic acid and arsenic trioxide treatment and their mechanisms of action on acute promyelocytic leukemia. Acute promyelocytic leukemia (APL) is a hematological malignancy driven by a chimeric oncoprotein containing the C terminus of the retinoic acid receptor-a (RARa) fused to an N-terminal partner, most commonly promyelocytic leukemia protein (PML). Mechanistically, PML-RARa acts as a transcriptional repressor of RARa and non-RARa target genes and antagonizes the formation and function of PML nuclear bodies that regulate numerous signaling pathways. The empirical discoveries that PML-RARa–associated APL is sensitive to both all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO), and the subsequent understanding of the mechanisms of action of these drugs, have led to efforts to understand the contribution of molecular events to APL cell differentiation, leukemia-initiating cell (LIC) clearance, and disease eradication in vitro and in vivo. Critically, the mechanistic insights gleaned from these studies have resulted not only in a better understanding of APL itself, but also carry valuable lessons for other malignancies.
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影响因子：
20.3
作者：
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通讯作者：
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DOI：
10.1073/pnas.88.5.1977
发表时间：
1991-03-01
影响因子：
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作者：
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