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Lymphoid enhancer-binding factor 1 (LEF-1): a favorable prognostic factor in adult acute myeloid leukemia in Egyptian patients
Egyptian Journal of Medical Human Genetics ( IF 1.2 ) Pub Date : 2020-07-22 , DOI: 10.1186/s43042-020-00073-5
Botheina Ahmed Thabet Farweez , Nahela Ahmed Shalaby , Doaa Ahmed Gamal Eissa , Raghda El Sayed Abdel Monem Galal , Nashwa El-khazragy , Shaimaa Abdelmalik Pessar

Canonical wingless-type (Wnt) signaling is a crucial pathway involved in normal hematopoiesis and the self-renewal process of hematopoietic stem cells. Deregulation of this pathway has been associated with different subtypes of leukemia. Lymphoid enhancer-binding factor 1 (LEF-1) is a major transcription factor of this pathway and plays a pivotal role in lymphoid differentiation and granulopoiesis. High LEF-1 expression has been reported as a prognostic marker in several types of adult hematological malignancies. We aimed to assess the prognostic utility of LEF-1 expression in adult de novo acute myeloid leukemia (AML) Egyptian patients in continuation of our previous work. LEF-1 expression was analyzed by real-time polymerase chain reaction (PCR) in 30 adults with newly diagnosed AML and remeasured at day 28 after induction therapy with the assessment of remission status. Patients were classified according to median expression level into high and low LEF-1 expression groups. LEF-1 levels were dramatically decreased following successful induction therapy. Also, high LEF-1 expression patients had a better response to therapy with better overall survival. ROC curve analysis of LEF-1 expression yielded a cutoff value of < 10.11 log10 (sensitivity of 90.48% and specificity of 100%) for predicting poor outcome. Univariate logistic regression analysis showed that for every log10 increase in the LEF-1 expression level, the chance of the patient to achieve hematological remission was increased by 2.29 folds. Our study showed preliminary results that overexpression of LEF-1 is a favorable prognostic factor in newly diagnosed adult AML patients. The prognostic value of LEF-1 could suggest its utility for further risk classifications of AML and potentiality for being a target for therapy.

中文翻译:

淋巴增强子结合因子 1 (LEF-1):埃及患者成人急性髓系白血病的有利预后因素

经典无翼型 (Wnt) 信号传导是参与正常造血和造血干细胞自我更新过程的关键途径。该途径的失调与不同亚型的白血病有关。淋巴增强子结合因子 1 (LEF-1) 是该途径的主要转录因子,在淋巴分化和粒细胞生成中起关键作用。据报道,高 LEF-1 表达是几种类型的成人血液系统恶性肿瘤的预后标志物。我们旨在评估 LEF-1 表达在成人新发急性髓性白血病 (AML) 埃及患者中的预后效用,以继续我们之前的工作。通过实时聚合酶链反应 (PCR) 在 30 名新诊断的 AML 成人中分析 LEF-1 表达,并在诱导治疗后第 28 天重新测量并评估缓解状态。根据中位表达水平将患者分为高LEF-1表达组和低LEF-1表达组。诱导治疗成功后,LEF-1 水平显着降低。此外,高 LEF-1 表达患者对治疗的反应更好,总生存期更好。LEF-1 表达的 ROC 曲线分析产生 < 10.11 log10 的临界值(90.48% 的敏感性和 100% 的特异性)用于预测不良结果。单变量逻辑回归分析显示,LEF-1 表达水平每增加 log10,患者达到血液学缓解的机会增加 2.29 倍。我们的研究初步结果表明,LEF-1 的过度表达是新诊断的成人 AML 患者的有利预后因素。LEF-1 的预后价值可能表明其可用于 AML 的进一步风险分类和作为治疗目标的潜力。
更新日期:2020-07-22
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