Department of Genomics of Adaptive Immunity, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, 117997 Moscow, Russia.
Center of Life Sciences, Skolkovo Institute of Science and Technology, 121205 Moscow, Russia.
Int J Mol Sci. 2022 Feb 3;23(3):1756. doi: 10.3390/ijms23031756.
Retroelements (RE) have been proposed as important players in cancerogenesis. Different cancer types are characterized by a different level of tumor-specific RE insertions. In previous studies, small cohorts of hematological malignancies, such as acute myeloid leukemia, multiple myeloma, and chronic lymphocytic leukemia have been characterized by a low level of RE insertional activity. Acute lymphoblastic leukemia (ALL) in adults and childhood acute leukemias have not been studied in this context. We performed a search for new RE insertions (Alu and L1) in 44 childhood ALL, 14 childhood acute myeloid leukemia, and 14 adult ALL samples using a highly sensitive NGS-based approach. First, we evaluated the method sensitivity revealing the 1% detection threshold for the proportion of cells with specific RE insertion. Following this result, we did not identify new tumor-specific RE insertions in the tested cohort of acute leukemia samples at the established level of sensitivity. Additionally, we analyzed the transcription levels of active L1 copies and found them increased. Thus, the increased transcription of active L1 copies is not sufficient for overt elevation of L1 retrotranspositional activity in leukemia.
逆转录元件(RE)被认为是癌症发生的重要因素。不同类型的癌症具有不同水平的肿瘤特异性 RE 插入。在之前的研究中,小部分血液系统恶性肿瘤,如急性髓系白血病、多发性骨髓瘤和慢性淋巴细胞白血病,其 RE 插入活性水平较低。成人急性淋巴细胞白血病(ALL)和儿童急性白血病尚未在此背景下进行研究。我们使用高度敏感的基于 NGS 的方法在 44 例儿童 ALL、14 例儿童急性髓系白血病和 14 例成人 ALL 样本中搜索新的 RE 插入(Alu 和 L1)。首先,我们评估了方法的灵敏度,揭示了具有特定 RE 插入的细胞比例的 1%检测阈值。根据这一结果,我们在既定灵敏度水平的急性白血病样本测试队列中未发现新的肿瘤特异性 RE 插入。此外,我们分析了活跃 L1 拷贝的转录水平,发现其增加。因此,活跃 L1 拷贝的转录增加不足以导致白血病中 L1 逆转座活性的明显升高。