不同 PARP1、PARP2、PARP3 和 TRPM2 基因在急性髓系白血病细胞中的表达调控。
Different regulation of PARP1, PARP2, PARP3 and TRPM2 genes expression in acute myeloid leukemia cells.
机构信息
Department of Clinical Genetics, Medical University of Lublin, 11 Radziwillowska Str, 20-080, Lublin, Poland.
Department of Public Health, Faculty of Health Sciences, Medical University of Lublin, 1 Chodźki Str, 20-093, Lublin, Poland.
出版信息
BMC Cancer. 2020 May 18;20(1):435. doi: 10.1186/s12885-020-06903-4.
BACKGROUND
Acute myeloid leukemia (AML) is a heterogenic lethal disorder characterized by the accumulation of abnormal myeloid progenitor cells in the bone marrow which results in hematopoietic failure. Despite various efforts in detection and treatment, many patients with AML die of this cancer. That is why it is important to develop novel therapeutic options, employing strategic target genes involved in apoptosis and tumor progression.
METHODS
The aim of the study was to evaluate PARP1, PARP2, PARP3, and TRPM2 gene expression at mRNA level using qPCR method in the cells of hematopoietic system of the bone marrow in patients with acute myeloid leukemia, bone marrow collected from healthy patients, peripheral blood of healthy individuals, and hematopoietic stem cells from the peripheral blood after mobilization.
RESULTS
The results found that the bone marrow cells of the patients with acute myeloid leukemia (AML) show overexpression of PARP1 and PARP2 genes and decreased TRPM2 gene expression. In the hematopoietic stem cells derived from the normal marrow and peripheral blood after mobilization, the opposite situation was observed, i.e. TRPM2 gene showed increased expression while PARP1 and PARP2 gene expression was reduced. We observed positive correlations between PARP1, PARP2, PARP3, and TRPM2 genes expression in the group of mature mononuclear cells derived from the peripheral blood and in the group of bone marrow-derived cells. In AML cells significant correlations were not observed between the expression of the examined genes. In addition, we observed that the reduced expression of TRPM2 and overexpression of PARP1 are associated with a shorter overall survival of patients, indicating the prognostic significance of these genes expression in AML.
CONCLUSIONS
Our research suggests that in physiological conditions in the cells of the hematopoietic system there is mutual positive regulation of PARP1, PARP2, PARP3, and TRPM2 genes expression. PARP1, PARP2, and TRPM2 genes at mRNA level deregulate in acute myeloid leukemia cells.
背景
急性髓系白血病（AML）是一种异质性致命疾病，其特征是骨髓中异常髓系祖细胞的积累，导致造血功能衰竭。尽管在检测和治疗方面做出了各种努力，但许多 AML 患者仍死于这种癌症。因此，开发新的治疗方法非常重要，需要采用涉及细胞凋亡和肿瘤进展的战略靶标基因。
方法
本研究的目的是使用 qPCR 方法评估造血系统骨髓细胞中 PARP1、PARP2、PARP3 和 TRPM2 基因在 mRNA 水平的表达，这些细胞取自急性髓系白血病患者、健康患者的骨髓、健康个体的外周血以及动员后外周血中的造血干细胞。
结果
结果发现，急性髓系白血病（AML）患者的骨髓细胞中 PARP1 和 PARP2 基因过表达，而 TRPM2 基因表达下调。在正常骨髓和动员后外周血来源的造血干细胞中观察到相反的情况，即 TRPM2 基因表达增加，而 PARP1 和 PARP2 基因表达减少。我们观察到来自外周血的成熟单核细胞组和骨髓来源细胞组中 PARP1、PARP2、PARP3 和 TRPM2 基因表达之间存在正相关。在 AML 细胞中，未观察到这些基因表达之间的显著相关性。此外，我们发现 TRPM2 表达下调和 PARP1 过表达与患者总生存期缩短相关，表明这些基因表达在 AML 中具有预后意义。
结论
我们的研究表明，在生理条件下，造血系统细胞中 PARP1、PARP2、PARP3 和 TRPM2 基因的表达存在相互正向调节。PARP1、PARP2 和 TRPM2 基因在急性髓系白血病细胞中在 mRNA 水平上失调。
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