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Abstract Acute myeloid leukemia accounts for 1.45% of all cancers and for 32% of newly diagnosed acute leukemia in Egypt. Treatment of AML strategies needs to be developed by identifying new markers and targets for treatment because about 50% of patients die due to aggressive disease and the percentage of old patients that survive more than 5 years with this disease is less than 10%. It is required to identify good molecular markers that precisely characterize this disease MUC4 gene expression is associated with poor outcomes in many solid tumors including pancreatic, colon and stomach cancers and is regarded as a prognostic factor in these tumors and its high expression of MUC4 is regarded as one from the important prognostic factors of chemotherapeutic failure in high risk pediatric B-ALL. LMWPTP (ACP1) gene overexpression was regarded as a potential marker for primary stages of tumorigenesis. It is overexpressed in many solid tumors as colon, prostate, colorectal cancers and neuroblastoma and this overexpression is accompanied by worse treatment outcome and low survival rate. Also it is involved in the presence of chemoresistance phenotype in CML and melanoma cancer. Summary 96 Therefore, this study was designed to investigate the expression levels of ACP1 and MUC4 genes in adult and pediatric patients with AML, and evaluate their diagnostic and prognostic values in this disease. This study was conducted on 146 subjects recruited from the adult and pediatric medical oncology department of the National Cancer Institute, Cairo University from May 2016 to May 2017. AML patients were fully diagnosed by clinical and laboratory examinations before conducting the study. The study was approved by the ethical committee, review board of NCI, Cairo University in accordance with Helsinki guidelines for the protection of human subjects. Written informed consent was obtained from all subjects. 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 1 st chemotherapy induction Summary 97 Follow up was done after 1st induction period till death or last visit or end of study in October 2019. 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 MUC4 gene compared to GAPDH as a reference gene using Real time PCR. Quantitative gene expression analysis of ACP1 gene compared to GAPDH as a reference gene using Real time PCR. The results of the study can be summarized as follow: BM expression level of MUC4 was significantly overexpressed in adult and pediatric AML patients when compared to the control group (p = 0.005, p<0.001 respectively). For adults, MUC4 gene expression level in BM was significantly associated with AML treatment response as its expression level was lower in the persistent remission group compared to the resistant or the relapse groups (p=0.001), also good responders have high expression level of MUC4 Summary 98 in the good responders in comparison to the poor responders to chemotherapy (p<0.001). For pediatric group, there was no difference of BM MUC4 expression levels between good and poor responders. Kaplan-Meier test elucidated that shorter OS and DFS in adults were significantly associated with high expression levels of MUC4 in BM (p=0.011, p=0.006 respectively). Univariate and multivariate Cox regression models assured that there were significant relationships between shorter OS and DFS with high expression levels of MUC4. High expression levels of MUC4 can be regarded as an independent prognostic factor for poorer OS and DFS in adult AML patients. But in pediatrics, OS wasn’t associated with MUC4 expression level. There was no significant association between MUC4 levels and sex, BM blasts, HB, PLT count, TLC, FLT3-ITD mutation or karyotyping classification in adult and pediatric patients. In pediatrics, older patients have overexpression of MUC4 levels when compared to younger patients (p=0.032). Expression levels of ACP1 was significantly increased in AML patients (adult & pediatrics) when compared to control. Summary 99 No significant association was found between ACP1 expression level and treatment response or final outcome. In addition, survival analysis by Kaplan-Meier test revealed that ACP1 expression can’t be used to predict OS in AML patients either for adults or pediatrics. DFS also wasn’t associated with ACP1 expression in adults. There was no significant association between ACP1 levels and sex, age, BM blasts, HB, PLT count, TLC, FLT3-ITD mutation or karyotyping classification. |