Abstract:
Acute myeloid leukemia (AML) shows multiple chromosomal translocations & point mutations which can be used to refine risk-adapted therapy in AML patients. Ecotropic viral integration site-1 (EVI-1) & myocyte enhancer factor 2 C gene (MEF2C) are key regulatory transcription factors in hematopoiesis and leukemogenesis & both drive immune escape. This prospective study involved 80 adult de novo AML patients recruited from Oncology Center, Mansoura University, between March 2019 and July 2021. The MEF2C and EVI1 expression were measured using a Taqman probe-based qPCR assay. The results revealed that EVI1 and MEF2C expression were significantly elevated in AML patients as compared to control subjects (p = 0.001. 0.007 respectively). Aberrant expressions of EVI1 and MEF2C showed a significant negative correlation with hemoglobin levels (p = 0.034, 0.025 respectively), & bone marrow blasts (p = 0.007, 0.002 respectively). 11q23 translocation was significantly associated with EVI1 and MEF2C (p = 0.004 and 0.02 respectively). Also, t (9;22) was significantly associated with EVI1 and MEF2C (p = 0.01 and 0.03 respectively), higher expression of EVI1 and MEF2C were significantly associated with inferior outcome after induction therapy (p = 0.001 and 0.018 respectively) and shorter overall survival (p = 0.001, 0.014 respectively). In conclusion, EVI1 & MEF2C were significantly expressed in AML cases. EVI1 & MEF2C overexpression were significantly associated with 11q23 rearrangements and t (9;22) and were indicators for poor outcome in adult AML patients; These results could be a step towards personalized therapy in those patients.
摘要:
急性髓性白血病(AML)显示多个染色体易位和点突变,可用于改善AML患者的风险适应疗法。亲合病毒整合位点1(EVI-1)和肌细胞增强因子2C基因(MEF2C)是造血和白血病发生中的关键调节转录因子,两者都驱动免疫逃逸。这项前瞻性研究涉及80名从肿瘤学中心招募的成人初发AML患者,曼苏拉大学,2019年3月至2021年7月。使用基于Taqman探针的qPCR测定法测量MEF2C和EVI1表达。结果显示,与对照组相比,AML患者的EVI1和MEF2C表达显着升高(p=0.001。分别为0.007)。EVI1和MEF2C的异常表达与血红蛋白水平呈显著负相关(p=0.034,0.025)。&骨髓母细胞(分别为p=0.007,0.002)。11q23易位与EVI1和MEF2C显著相关(p分别为0.004和0.02)。此外,t(9;22)与EVI1和MEF2C显著相关(p分别为0.01和0.03),较高的EVI1和MEF2C表达与诱导治疗后较差的结局(分别为p=0.001和0.018)和较短的总生存期(分别为p=0.001,0.014)显著相关.总之,EVI1和MEF2C在AML病例中显著表达。EVI1和MEF2C过表达与11q23重排和t(9;22)显着相关,并且是成年AML患者预后不良的指标;这些结果可能是这些患者个性化治疗的一步。