Sohani Mahsa, Rostami Shahrbano, Azad Mehdi, Hojjatipour Tahereh, Chahardouli Bahram, Alizadeh Shaban
Department of Hematology and Blood Banking, School of Allied Medical Sciences, Tehran University of Medical Sciences, Tehran, Iran.
Hematology, Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Int J Hematol Oncol Stem Cell Res. 2021 Jan 1;15(1):7-14. doi: 10.18502/ijhoscr.v15i1.5245.
: Although the precise pathogenesis of acute lymphoblastic leukemia (ALL) remains unclear, studying gene-regulating mechanisms during ALL pathogeneses may shed light on the underlying mechanisms driving malignant behavior. There is some evidence showing the promoter hypermethylation and silencing of RASSF1A tumor suppressor gene in ALL cells; however, there is a lack of evidence for whether the gene indeed alters during different phases of ALL or in response to therapy. Thus, the current study aimed to clarify this issue using groups of adult ALL patients who have been scarcely investigated regarding expression levels and promoter methylation status. : In this case/control study, the expression levels and methylation status of the gene promoter was evaluated using quantitative real-time PCR and methylation-specific PCR (MSP), respectively in adults with ALL. The study included peripheral blood of patients with newly diagnosed ALL (n=10), complete remission (CR) (n=10), or relapse (n=10), and 10 control samples from healthy individuals. : MSP results revealed an unmethylated status for almost all patients and control samples, except a case with relapsing ALL, which showed a hemimethylated pattern. RASSF1A also showed no difference in terms of gene expression in the patients compared with the control group (>0.05). : The results revealed an up-regulation of RASSF1A tumor suppressor in adult ALL patients experiencing CR, suggesting this to be a marker of therapy response. However, further investigations using more sensitive methylation detecting tools with larger sample sizes may better clarify the involvement of the promoter methylation of RASSF1A in these patients.
尽管急性淋巴细胞白血病(ALL)的确切发病机制尚不清楚,但研究ALL发病过程中的基因调控机制可能有助于揭示驱动恶性行为的潜在机制。有证据表明ALL细胞中RASSF1A肿瘤抑制基因的启动子高甲基化和沉默;然而,缺乏关于该基因在ALL不同阶段或对治疗的反应中是否确实发生改变的证据。因此,本研究旨在通过对成年ALL患者组进行研究来阐明这一问题,此前针对这些患者的表达水平和启动子甲基化状态几乎没有进行过研究。
在这项病例对照研究中,分别使用定量实时PCR和甲基化特异性PCR(MSP)评估了成年ALL患者中该基因启动子的表达水平和甲基化状态。该研究纳入了新诊断ALL患者(n = 10)、完全缓解(CR)患者(n = 10)或复发患者(n = 10)的外周血,以及来自健康个体的10个对照样本。
MSP结果显示,几乎所有患者和对照样本均为未甲基化状态,但有1例复发ALL患者显示为半甲基化模式。与对照组相比,患者组中RASSF1A的基因表达也没有差异(>0.05)。
结果显示,处于CR期的成年ALL患者中RASSF1A肿瘤抑制因子上调,提示这可能是治疗反应的一个标志物。然而,使用更敏感的甲基化检测工具并扩大样本量进行进一步研究,可能会更好地阐明RASSF1A启动子甲基化在这些患者中的作用。