Department of Laboratory Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Medical Biotechnology and Laboratory Science, Chang Gung University, Taoyuan, Taiwan.
Department of Laboratory Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; Clinical Informatics and Medical Statistics Research Center, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Biomed J. 2023 Apr;46(2):100518. doi: 10.1016/j.bj.2022.03.003. Epub 2022 Mar 17.
Changes in ABO blood type caused by a gradual decrease in antigen expression have been found in patients with acute myeloid leukemia (AML). Studies have indicated that alteration of ABO gene methylation accounts for 50% of acquired weak ABO antigen expression in patients with leukemia. However, the molecular mechanisms contributing to the remaining 50% of cases are unknown. We hypothesize that deregulation of miRNA is correlated with weak ABO antigen expression in patients with AML.
Blood samples of 19 patients with AML and 12 healthy controls were collected, in which the blood type was not changed in these AML patients. Flow cytometric analysis was applied to measure the ABO antigen expression titer among AML patients and controls. A total of 18 leukemia-related miRNAs were analyzed via quantitative real-time polymerase chain reactions.
We found that miRNA profiles were correlated with the AML patients, especially in those who had constant or weakened ABO antigen expressions. Compared with healthy controls, the miR-16 and miR-451 expression were significantly lower in either AML cases with weak ABO antigen expressions (p = 0.003, p = 0.028, respectively) or AML cases with constant ABO antigen expressions (p = 0.043, p = 0.040, respectively). Although not statistically significant, decreasing trends in the miR-451 and miR-16 expressions in the AML patients with weakened ABO were observed compared to those with constant ABO antigens. The weak ABO antigen expression might correlate with miRNAs, especially miR-16 and miR-451.
This study indicated that decreasing in miR-16 and miR-451 was associated with AML and AML with weakened ABO expression. In the future, we will continue to include more cases and exclude the others factor influencing ABO antigen expression, promoter methylation and oxidative stress, to replicate the results of this study and investigate the underlying mechanism of decreasing miR-16 and miR-451 in AML patients with varied ABO antigen expression levels.
在急性髓细胞白血病(AML)患者中发现 ABO 血型发生抗原表达逐渐下降的变化。研究表明,白血病患者获得性弱 ABO 抗原表达的 50%归因于 ABO 基因甲基化的改变。然而,导致其余 50%病例的分子机制尚不清楚。我们假设 miRNA 的失调与 AML 患者的弱 ABO 抗原表达有关。
收集了 19 例 AML 患者和 12 例健康对照者的血液样本,这些 AML 患者的血型在这些患者中没有改变。采用流式细胞术分析测量 AML 患者和对照组的 ABO 抗原表达滴度。通过定量实时聚合酶链反应分析了 18 种与白血病相关的 miRNA。
我们发现 miRNA 谱与 AML 患者相关,尤其是在那些具有恒定或减弱的 ABO 抗原表达的患者中。与健康对照组相比,弱 ABO 抗原表达的 AML 患者(p=0.003,p=0.028)或恒定 ABO 抗原表达的 AML 患者(p=0.043,p=0.040)中 miR-16 和 miR-451 的表达均明显降低。尽管没有统计学意义,但与具有恒定 ABO 抗原的患者相比,具有减弱的 ABO 抗原表达的 AML 患者中 miR-451 和 miR-16 的表达呈下降趋势。弱的 ABO 抗原表达可能与 miRNA 相关,尤其是 miR-16 和 miR-451。
本研究表明,miR-16 和 miR-451 的减少与 AML 和 AML 伴减弱的 ABO 表达相关。在未来,我们将继续纳入更多病例,并排除其他影响 ABO 抗原表达、启动子甲基化和氧化应激的因素,以复制本研究的结果,并研究在不同 ABO 抗原表达水平的 AML 患者中 miR-16 和 miR-451 减少的潜在机制。