Younesian Samareh, Shahkarami Sepideh, Ghaffari Parisa, Alizadeh Shaban, Mehrasa Roya, Ghavamzadeh Ardeshir, Ghaffari Seyed H
Hematology, Oncology and Stem Cell Transplantation Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran; Department of Hematology, School of Allied Medical Sciences, International Campus, Tehran University of Medical Sciences, Tehran, Iran.
Hematology, Oncology and Stem Cell Transplantation Research Center, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran; Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Leuk Res. 2017 Oct;61:33-38. doi: 10.1016/j.leukres.2017.08.016. Epub 2017 Aug 30.
The Hypermethylation of Ras association domain family (RASSF) often plays a key role in malignant progression of solid tumors; however, their impact on the prognosis and survival of adult ALL patients remain elusive.
The frequency of the promoter methylation pattern of RASSF6 and RASSF10 were analyzed in the peripheral blood (PB) samples taken at the time of diagnosis of 45 ALL patients. The methylation-specific PCR (MSP) assay was used to detect the DNA methylation patterns.
RASSF6 was frequently hypermethylated in patients diagnosed with pre-B-ALL (90.9%) and B-ALL (87.5%), followed by T-ALL (66.7%); whereas, RASSF10 methylation was more confined to T-ALL (80%) as compared to B-ALL (25%) and pre-B ALL (9.1%) patients. Moreover, hypermethylation of RASSF6 was significantly associated with a poor prognosis and shorter overall survival (OS) in patients with pre-B-ALL (log-rank test; P=0.041).
RASSF6 and RASSF10 were frequently hypermethylated in the samples at the time of diagnosis of adult ALL patients. Our study represents the first report of methylation of RASSF6 at a high frequency in patients with pre-B ALL. Furthermore, hypermethylation of RASSF6 was significantly associated with inferior overall survival in pre-B ALL patients. It may suggest that the frequent epigenetic inactivation of RASSF6 plays an important role in the pathogenesis and progression of pre-B-ALL.
Ras 关联结构域家族（RASSF）的高甲基化在实体瘤的恶性进展中常起关键作用；然而，它们对成人急性淋巴细胞白血病（ALL）患者预后和生存的影响仍不明确。
分析了 45 例 ALL 患者诊断时采集的外周血（PB）样本中 RASSF6 和 RASSF10 启动子甲基化模式的频率。采用甲基化特异性 PCR（MSP）检测法检测 DNA 甲基化模式。
在诊断为前 B 细胞 ALL（90.9%）和 B 细胞 ALL（87.5%）的患者中，RASSF6 经常发生高甲基化，其次是 T 细胞 ALL（66.7%）；而与 B 细胞 ALL（25%）和前 B 细胞 ALL（9.1%）患者相比，RASSF10 甲基化更多局限于 T 细胞 ALL（80%）。此外，RASSF6 的高甲基化与前 B 细胞 ALL 患者的不良预后和较短总生存期（OS）显著相关（对数秩检验；P = 0.041）。
在成人 ALL 患者诊断时的样本中，RASSF6 和 RASSF10 经常发生高甲基化。我们的研究是前 B 细胞 ALL 患者中 RASSF6 高频甲基化的首次报道。此外，RASSF6 的高甲基化与前 B 细胞 ALL 患者较差的总生存期显著相关。这可能表明 RASSF6 频繁的表观遗传失活在前 B 细胞 ALL 的发病机制和进展中起重要作用。
