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Abstract
Drug resistance is one of the most significant challenges facing clinicians who treat malignancies .Despite major advances in cancer chemotherapy, many patients develop recurrent disease after initially responding well to therapies.
Over the last 20 years, experimental models and clinical research have identified several causes of multidrug resistance (MDR) in tumors. This improved understanding of the mechanisms involved in multidrug resistance has permitted the development of new thera¬peutic strategies.
A representative cause of MDR is the expression of MDR1 gene and its product, P-glycoprotein, on the cell surface membrane.
P-glycoprotein acts as an efflux pump excreting chemotherapeutic agents from the cells before they can exert their cytotoxic effects.
P-glycoprotein contributes to chemotherapy failure in acute leukemia. However, the exact prognostic significance of this resistant mechanism is still unclear, mostly due to problems in the methods of P-gp detection.
The main purpose of this study was to investigate and clarify the prognostic impact of P-glycoprotein expression level on the response to induction chemotherapy in children with de-novo acute leukemia and to study the relationship between P-glycoprotein and demographic, clinical and laboratory data of the examined patients.
The present study included 55 subjects classified into three groups:
Group I: 35 newly diagnosed children with acute leukemia. Among them 27(77.1%) were diagnosed as ALL and 8(22.9%) were diagnosed as AML.
Group II: 10 unrelated children with acute leukemia in relapse. Among them 7(70%) were ALL and 3(30%) were AML.
Group III: 10 age and sex matched healthy children were included in the study as a control group.
All members of the study were subjected to the following:
1- Full history taking.
2- Thorough clinical examination.
3- Routine laboratory examination:
Including complete blood picture, bone marrow aspiration and examination, immunophenotyping of marrow samples, Liver and kidney function tests, serum LDH, serum uric acid, serum electrolytes and coagulation profile.
4- Estimation of P-glycoprotein (P-gp) expression level by flowcytometry using Anti-p-glycoprotein monoclonal antibody.
The results of the present work showed:
1- No relationship between P.gp expression level and outcome of induction chemotherapy in ALL and AML.
2- No significant difference between de-novo and relapse patients regarding P-glycoprotein expression.
3- No significant difference between ALL and AML patients regarding P-glycoprotein expression.
4- No relationship between P.gp expression level and demographic and clinical data of patients (age and sex)
5- No relationship between P.gp expression level and laboratory data of patients (CBC findings, FAB subtypes and immunophenotypic subtypes)
CONCLUSION
There is no relationship between P-glycoprotein expression and outcome of induction chemotherapy, demographic, clinical and laboratory data of the examined patients concluding that P-glycoprotein has no prognostic significance in childhood acute leukemia.