a Department of Biology and.
c Division of Hematology, Department of Medicine, University of Ottawa, Ottawa, Canada; and.
Radiat Res. 2018 Feb;189(2):213-218. doi: 10.1667/RR14897.1. Epub 2017 Dec 12.
The only curative treatment option for relapsed patients with acute myeloid leukemia (AML) is allogeneic stem cell transplantation. Depletion of hematopoietic stem cells and leukemic blast cells is achieved through the systemic administration of DNA damaging agents, including total-body irradiation (TBI) prior to transplantation. Since other tissues are radiosensitive, the identification of biomarkers could facilitate the management of additional toxicities. Buccal keratinocytes are readily accessible and could provide a source of cells for RNA analysis. In this study, we obtained miRNAs and mRNAs from daily buccal swabs collected from patients undergoing allogeneic stem cell transplantation. Unexpectedly, there was no prominent p53-induced mRNA or miRNA response in these samples, despite the fact that the p53 pathway is a well-characterized radiation-inducible response. Instead, the expression of mRNAs encoding p53 and cytokeratin 14 (TP53 and KRT14, respectively) decreased precipitously within hours of the first radiation treatment. These patients went on to develop oral mucositis, however, it is unclear whether TP53 and/or KRT14 expression are predictive of this adverse event. Larger scale analysis of buccal epithelial samples from patients undergoing allogeneic stem cell transplantation appears to be warranted.
对于复发的急性髓细胞白血病 (AML) 患者，唯一的治愈性治疗选择是异体干细胞移植。通过全身给予 DNA 损伤药物，包括移植前全身照射 (TBI)，实现造血干细胞和白血病母细胞的耗竭。由于其他组织对辐射敏感，因此鉴定生物标志物可以帮助管理其他毒性。颊上皮细胞容易获得，并且可以为 RNA 分析提供细胞来源。在这项研究中，我们从接受异体干细胞移植的患者每天采集的颊拭子中获得了 miRNA 和 mRNA。出乎意料的是，尽管 p53 途径是一种特征明确的辐射诱导反应，但这些样本中并没有明显的 p53 诱导的 mRNA 或 miRNA 反应。相反，编码 p53 和角蛋白 14（分别为 TP53 和 KRT14）的 mRNA 的表达在第一次放射治疗后数小时内急剧下降。这些患者随后发生了口腔粘膜炎，但尚不清楚 TP53 和/或 KRT14 表达是否可预测这种不良事件。似乎有必要对接受异体干细胞移植的患者的颊上皮样本进行更大规模的分析。
