الفهرس 
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Abstract
A major issue in the treatment of acute myeloid leukemia (AML) is resistance to chemotherapeutic drugs. Many patients fail to respond to chemotherapy and others relapse with resistant disease.
Several mechanisms of drug resistance have been identified. One of these is the over expression of adenosine triphosphate binding cassette (ABC)-transporter proteins that function as drug efflux pumps. A number of recent studies showed that ABC-transporters confer resistance not only against classical chemotheraputic drugs but also against modern targeted therapies. Furthermore, some targeted drugs interact with ABC-transporters by inhibition or induction.
The best-characterized drug efflux pump is the permeability glycoprotein (P-gp), which is encoded by the multidrug resistance gene 1 (MDR1 or adenosine triphosphate binding cassette transporter B1 [ABCB1]). Expression of ABCB1 has long been identified as an independent adverse prognostic factor for complete remission and survival in adult patients with AML.
Other ABC-transporters that were shown to have clinical relevance in adult AML are the breast cancer resistance protein (BCRP, encoded by adenosine triphosphate binding cassette transporter G2 [ABCG2]). Many studies suggested that adenosine triphosphate binding cassette transporter G2 is associated with response to therapy.
Co-expression of multiple ABC transporters, rather than a single transporter, plays a vital role in the MDR of AML and contributes to a worse
prognosis. Therefore, detecting ABC transporters in de novo AML patients may help to predict prognosis.
Most importantly, ways to inhibit these MDR genes such as through RNA interference of the ABC transporters and the modification of miRNA epigenetic regulation, etc. still need to be explored but should not be limited to the inhibition of a single transporter. Instead, transporters should be targeted to overcome MDR.
The aim of the study was to analyze prognostic relevance of co-expression of ABCB1 transporter and ABCG2 transporter in newly diagnosed AML patients and their relation to response to induction treatment regimen
The present study was carried out on fourty acute myeloid leukemia patients admitted to hematology department, Alexandria main university hospitals and thirty healthy subjects as a control group. All patients and controls were matched in the demographic criteria regarding age and sex.
The results summarized that:
The median age of AML patients at presentation was 38.9 years with females to males ratio= 1.06:1.
This study revealed that, of all AML patients, 50% of cases had normal cytogenetics.
Negative results of both CD 243 and CD 338 expression in patients who achieved complete response after induction chemotherapy (p value 0.035, 0.014 respectively).
CD 243 was not affected by FAB subtype (p value = 0.676), Blast count (p value < 0.05) nor WBCS (P value = 0.747). Yet it was correlated with cytogenetics (P value 0.001) and treatment response (P value = 0.035). on the other hand, CD 338 was not affected by FAB subtype (p value = 0.178), Blast count (p value < 0.05) nor WBCS (P value = 0.655). Yet it was correlated with cytogenetics (P value 0.037) and treatment response (P value = 0.014)
It is concluded from this study that co-expression of CD 243(ABCB1) and CD 338 (ABCG2) in newly diagnosed AML patients is positively correlated with induction treatment response, thus it is suggested that routine measurement of both CD markers as prognostic elements is recommended and ABC inhibitors could be added to the present combination therapies. Further studies are recommended to elucidate correlation between co-expression of ABC transporters and response to treatment and initiation of developmental trials on ABC inhibitors and its additive value on treatment response.