الفهرس 
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Abstract
Leukemia makes up 10% of the total cancer cases in Egypt, and among different types of leukemia, acute myeloid leukemia (AML) represents 16.9% of the cases (Zawam H 2018). Developing effective treatment strategies for AML is crucial, as approximately 50% of patients succumb to the aggressive nature of the disease, and the survival rate for elderly patients beyond five years is below 10%. Therefore, there is a pressing need to identify reliable molecular markers that accurately characterize this disease, which can aid in the development of targeted therapies.
High expression of the YBX1 gene is linked to unfavorable outcomes in various solid tumors such as pancreatic, colon, and stomach cancers. It is considered a prognostic factor in these types of tumors, and its elevated expression is recognized as an important predictor of chemotherapy resistance and treatment failure.
Therefore, the primary objective of this study was to examine the expression levels of YBX1 in both adult and pediatric AML patients and assess the significance of these levels as diagnostic and prognostic indicators for this disease.
A total of 145 participants were enrolled in this study, recruited from the adult and pediatric medical oncology department at the National Cancer Institute, Cairo University. The recruitment period for the study spanned from January 2017 to December 2017. Before the study commenced, all AML patients underwent thorough clinical and laboratory examinations to ensure accurate diagnosis. Ethical approval for the study was obtained from the review board and ethical committee of the National Cancer Institute, Cairo University, in accordance with the guidelines outlined in the Helsinki Declaration for the protection of human subjects. Prior to their participation, written informed consent was obtained from all individuals involved in the study.
All participants in this study were divided into four groups; (Ⅰ) Adult patients. (ⅠⅠ) Pediatric patients. (ⅠⅠⅠ) Adult healthy control. (ⅠV) Pediatric healthy control.
All patients were routinely subjected to:
• Full history and clinical examination.
• Hematological and biochemical laboratory investigations required for AML diagnosis (CBC, IPT, cytogenetic and molecular study).
• Defining the treatment response at Day 28 from starting 1st chemotherapy induction
• Follow up was done after 1st induction period till death or last visit or end of study.
• OS was measured from the date of entry into the study to death or last visit and DFS was defined as the duration from the date of CR achievement to death or relapse.
All subjects including patients and healthy donors were evaluated for:
• Quantitative gene expression analysis of YBX1 gene compared to ACTB as a reference gene using Real time PCR.
The results of the study can be summarized as follow:
• Bone Marrow expression level of YBX1 was significantly overexpressed in adult and pediatric AML patients when compared to the control group (p<0.001, p<0.001 respectively).
• Increased YBX1 expression level in adult AML patients associates with the presence of adverse genomics abnormalities (p= 0.036).
• YBX1 may be specifically highly expressed in bone marrow clones that express both CD4 and CD14 markers that may play a critical role in AML relapse development.
• In adult patients, the expression level of the YBX1 gene in the bone marrow (BM) was found to be significantly correlated with the response to AML treatment. Specifically, the persistent remission group exhibited lower expression levels of YBX1 compared to the resistant or relapse groups (p= 0.005). YBX1 is distinctively high in relapsed adult cases. In the pediatric patients, the pattern of YBX1 expression levels showed an inverse relationship. It was observed that the persistent remission group had higher expression levels of YBX1 (p= 0.041) compared to other groups.
• Kaplan-Meier test elucidated that shorter DFS in adults were significantly associated with high expression levels of YBX1 in BM (p= 0.004). Univariate and multivariate Cox regression models assured that there were significant relationships between shorter DFS with high expression levels of YBX1. However, pediatric patients with upregulated YBX1 showed good OS over downregulated patients (p= 0.015). High expression levels of YBX1 can be regarded as an independent prognostic factor for poorer DFS in adult AML patients and good OS in pediatric patients.
• There was no significant association between YBX1 levels and sex, BM blasts, HB, PLT count, TLC or FLT3-ITD mutation in adult and pediatric patients.