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Longterm follow-up of Pgp activity and molecular response in CML patients treated with imatinib mesylate

Chronic myelogenous leukemia (CML) is a type of myeloproliferative disease associated with a characteristic Philadelphia chromosome which can be detected by PCR for the bcr-abl fusion gene. The specific treatment includes the inhibitor of tyrosine kinase imatinib mesylate (IM) affecting downstream signaling from aberrant bcr-abl kinase. The multidrug resistance (MDR) influence the treatment outcome and the best known resistance mechanism is linked to the activity of membrane P- glycoprotein (Pgp) which catalyses drug efflux. The aim of this study was to asses the correlation between Pgp activity and molecular response to IM therapy. Pgp activity was analysed on flow cytometer by Rhodamine123. Results were expressed as mean fluorescence ratio RMF where RMF>1 reflects elevated Pgp function. Pgp status was compared to RT-PCR results for the presence of bcr-abl fusion gene which were expressed as: R1= complete molecular remission (PCR negative), R2= major molecular response (MMR) (<0, 1% BRC-ABL), R3= minimal molecular response (mMR) (0, 1-1% BRC-ABL) and R4= without response (>1% BRC-ABL). 19 CML patients were monitored trough 2004-2009 and their peripheral blood and bone marrow cells were analysed. Complete molecular remission was observed in 8 patients (42, 1%), MMR was evident in 2 patients (10, 50%), 2 patients had mMR (10, 50%) while 7 patients had no response (36, 90%). All R1 patients had low Pgp activity compared to R4 patients with relatively higher Pgp activity which points out the correlation between Pgp activity and molecular level of oncogene BRC-ABL chimeric genes (p<0, 05). In conclusion, Pgp activity test reflects the course of genetic changes during therapy pointing out the increased activity as unfavorable prognostic factor.

multidrug resistance ; Pgp activity ; Imatinib mesylate ; CML ; molecular response

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