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染色质修饰物 EHMT2/G9a 和 KDM2b 在急性髓系白血病中的表达及预后意义。

Expression and prognostic significance of chromatin modulators EHMT2/G9a and KDM2b in acute myeloid leukemia.

机构信息

Department of Biochemistry, Faculty of Science, Ain Shams University, Cairo, Egypt.

Department of Clinical Pathology, National Cancer Institute, Cairo University, Cairo, Egypt.

出版信息

J Cell Biochem. 2022 Aug;123(8):1340-1355. doi: 10.1002/jcb.30297. Epub 2022 Jun 13.

DOI:10.1002/jcb.30297
PMID:35696556
Abstract

Epigenetics factors are critical for normal cell function and their regulation is sensitive to malignancy development. EHMT2/G9a and KDM2b are key epigenetics players in different cancer types. However, their expression profiles and related consequences in acute myeloid leukemia (AML) patients have not been known yet. In addition to routine lab work, expression levels of EHMT2/G9a and KDM2b were determined in 110 adult and pediatric patients with De Novo AML. Relations between their expression and patients' clinical data were tested by statistical methods. EHMT2/G9a and KDM2b were highly expressed in AML patients against control cases and associated with the presence of adverse genomic alterations. In response to induction chemotherapy, EHMT2/G9a and KDM2b showed to be significantly high in resistant and relapsed patients in comparison to the complete remission group. KDM2b overexpression was associated with CD11c (integrin alpha X) downregulation. Kaplan-Meier analysis indicated that EHMT2/G9a and KDM2b overexpression was correlated with poor survival status in AML patients. We conclude that EHMT2/G9a and KDM2b expression levels could be used as independent prognostic factors for AML disease.

摘要

表观遗传因子对于正常细胞功能至关重要,其调控对恶性肿瘤的发生发展非常敏感。EHMT2/G9a 和 KDM2b 是不同癌症类型中的关键表观遗传调控因子。然而,它们在急性髓系白血病(AML)患者中的表达谱和相关后果尚不清楚。除了常规的实验室工作外,还在 110 名患有初发 AML 的成人和儿科患者中测定了 EHMT2/G9a 和 KDM2b 的表达水平。通过统计学方法测试了它们的表达与患者临床数据之间的关系。EHMT2/G9a 和 KDM2b 在 AML 患者中表达水平较高,与对照病例相比,与不良基因组改变的存在相关。与完全缓解组相比,在耐药和复发患者中,EHMT2/G9a 和 KDM2b 在诱导化疗后的表达水平明显升高。KDM2b 的过表达与 CD11c(整合素 alpha X)的下调有关。Kaplan-Meier 分析表明,EHMT2/G9a 和 KDM2b 的过表达与 AML 患者的不良生存状态相关。我们得出结论,EHMT2/G9a 和 KDM2b 的表达水平可以作为 AML 疾病的独立预后因素。

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