Mitogen-Activated Protein Kinase 2 Relevance for the in-vitro Chemo-Sensitivity and Clinical Response in Children with Acute Lymphoblastic Leukemia in Mansoura University Hospitals

M. Mortada, Asmaa El-Rakhawy, Ahmad Darwish, Nabil Adeb, G. Dahab
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Abstract

Background : Identification of different prognostic biomarker of pediatric acute lymphoblastic leukemia (ALL) permits more characterization of patient subgroups and helps the risk-adapted treatment strategies. Aim : Our study assessed the role of Mitogen-Activated Protein Kinase (ERK1/2) as a prognostic biomarker of pediatric ALL in MUH patients. Another aim is to detect the relevance of ERK1/2 for the in-vitro leukemic cells response to chemotherapeutic agents (Vincristine, L-asparaginase Dexamethasone and Doxorubicin). Material and Methods : ERK1/2 was measured in the bone marrow aspirates of 26 children with newly diagnosed ALL by ELISA technique. The MTT in vitro chemo-sensitivity assay was used to detect in-vitro leukemic cells response. Results: At diagnosis, the pERK 1/2 and tERK 1/2 are significantly higher in the HR gp than SR gp (p-value =0.000 & 0.003 respectively). While the pERK/tERK 1/2 ratio at diagnosis was significantly higher than that post induction in the patients of our study (p-value= 0.03) . A significant association was detected between in vitro chemo-sensitivity to vincristine, l-asparaginase, dexamethasone & doxorubicin and complete remission after induction therapy, respectively). Conclusion : Our results indicated that ERK1/2 could be considered as an independent predictor of complete remission. Besides, a significant positive correlation was detected between ERK 1/2 and in vitro leukemic cells response to the four chemotherapeutic agents at diagnosis.
丝裂原活化蛋白激酶 2 与曼苏尔大学医院急性淋巴细胞白血病患儿体外化疗敏感性和临床反应的关系
背景:鉴定小儿急性淋巴细胞白血病(ALL)的不同预后生物标志物可进一步确定患者亚群的特征,并有助于制定风险适应性治疗策略。目的:我们的研究评估了丝裂原活化蛋白激酶(ERK1/2)作为MUH患者小儿急性淋巴细胞白血病预后生物标志物的作用。另一个目的是检测ERK1/2与体外白血病细胞对化疗药物(长春新碱、L-天冬酰胺酶地塞米松和多柔比星)反应的相关性。材料与方法:采用 ELISA 技术检测 26 名新诊断为 ALL 的儿童骨髓穿刺液中的 ERK1/2。采用MTT体外化疗敏感性试验检测体外白血病细胞的反应。结果显示诊断时,HR gp的pERK 1/2和tERK 1/2明显高于SR gp(p值分别为0.000和0.003)。而在我们的研究中,患者诊断时的 pERK/tERK 1/2 比值明显高于诱导后的 pERK/tERK 1/2 比值(p 值= 0.03)。对长春新碱、l-天冬酰胺酶、地塞米松和多柔比星的体外化疗敏感性分别与诱导治疗后的完全缓解之间存在明显关联)。结论我们的研究结果表明,ERK1/2可被视为完全缓解的独立预测因子。此外,ERK 1/2与体外白血病细胞对诊断时的四种化疗药物的反应之间存在明显的正相关。
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