╨╧рб▒с>■  (*■   '                                                                                                                                                                                                                                                                                                                                                                                                                                                ье┴#`Ё┐Аbjbjmеmе8╧╧{      д╛╛╛╛╛╛╛╥zzzzО ╥М $жжжжжБББєїїїїїї$░ h N -╛сББсс ╛╛жж█F ЯЯЯс^╛ж╛жєЯсєЯЯ╛╛ЯжЪ ЁйUB%Х╦z?LЯ▀\ 0М ЯfЛ fЯf╛Я@Б0▒"Я╙яЄБББ  Х БББМ сссс╥╥╥╓д╥╥╥╓╥╥╥╛╛╛╛╛╛     Low levels of residual disease in CML are associated with low molecular level of oncogene BCR-ABL chimeric genes and low Pgp activity Ana Savi (1), Radmila Ajdukovi (2) , Maruaka Maruai-Vrsalovi (2), Ana Livun (2), Kreao Bendelja (1), Ivna Svoboda Beusan (1) (1) Institute of Immunology, (2) Clinical Hospital Dubrava , Zagreb, Croatia Imatinib mesylate (IM) therapy in chronic myelogenous leukemia (CML) patients can induce multidrug resistance (MDR) which is associated with poor treatment outcome. The best known resistance mechanism is associated with activity of P-glycoprotein (Pgp) membrane transporter. Twenty five patients were diagnosed with chronic phase CML at Clinical Hospital Dubrava and were monitored over the period of six years. In order to elucidate the mechanism of MDR induction we evaluated the effect of IM monotherapy by comparing the variations in the activity of Pgp pump with molecular response kinetics. Pgp activity of bone marrow and peripheral blood cells was assessed by flow cytometry and the results were expressed as the ratio of minimal and real pump activity . The kinetics of molecular response was measured by qRT-PCR method and the results were divided in 4 groups: R1= complete molecular remission, R2= major molecular response (MMR), R3= minimal molecular response (mMR) and R4= without response. Nine patients were in R1 (36, 0%), 2 in R2 (8,0%), 4 in R3 (16,0%) while 4 patients were in group R4. Two patients entered the study recently and are not evaluable . All R1 patients had low Pgp activity whereas the greatest activity increase was observed in R4 group. These results confirm the link between Pgp activity and molecular response. We conclude that rhodamine test of Pgp activity has clinical value and correlates with the  X Y j k z Э з ▒ № р ї S U ├ ф EG√ц╬╕зТ}ТgТ}Т}R}R}R}R}P}U(hr&ўh┴[ЭCJOJQJ^JaJmH sH +hr&ўh XUCJOJQJ^JaJmHnHu(hr&ўh╪j╤CJOJQJ^JaJmH sH (hr&ўh XUCJOJQJ^JaJmH sH  hr&ўh╪j╤CJOJQJ^JaJ+hr&ўh╖AwCJOJQJ^JaJmHnHu.hr&ўh╖Aw>*CJOJQJ^JaJmHnHu1hr&ўh╖Aw5БCJOJQJ\Б^JaJmHnHu  X Y Аўяяяяччх$a$gd╪j╤$a$gd╖Aw$a$gd╖AwА■BCR/ABL oncogene changes during therapy with IM, indicating that elevated Pgp activity adds as unfavorable prognostic factor. Ац╤═hсE(hr&ўh╪j╤CJOJQJ^JaJmH sH 1hr&ўh╪j╤B*CJOJQJ^JaJmH ph sH 61РhP:p╪j╤░В. ░╞A!░Й"░Й#РЙ$РЙ%░░─░─ Р─ЖЬV@ё V ╪j╤Normal dд╚$CJOJQJ^J_HaJmHsHtH >AЄ б> Zadani font odlomkaViє │V Obi na tablicaЎ4╓ l4╓aЎ .kЇ ┴. Bez popisa{    ЖЗ  XYz}Ш0ААШ@0ААШ@0ААШ@0ААШ@0ААШ0ААШ0ААШ0ААЖ  X}ъ╨00ъ╨00К╤00АК╤00А 00XА А А Ё8Ё@ё   АААўЁТЁЁ0Ё( Ё ЁЁB ЁS Ё┐╦  ?Ё  ╣HsTO║HsL[╗Hs,U▄jz}ъn~}C*Аurn:schemas-microsoft-com:office:smarttagsАmetricconverterА>*Аurn:schemas-microsoft-com:office:smarttags АPersonNameА ЙА4 inKreao Bendelja АProductID╝├HS√ИЛ(+▒║ }ЕЗ  W╬▀tvсь}333}} х G0сE XU╟?t╖Aw┴[ЭZ╠╪j╤═ўr&ўX} @АHHДPд▌HH(√{PP@P0@  Unknown            GРюЗz А Times New Roman5РАSymbol3&Рю Зz А Arial5&Рю ЗzaА Tahoma7&Рюяа{ @ЯCalibri"qИЁ─йЙ2ь&Й2ь&^ ^ БЁЙЙ┤┤ББ24dxx 2ГQЁHX)Ё ?т                     ╪j╤2  ЕLow levels of residual disease in CML are associated with low molecular level of oncogene BCR-ABL chimeric genes and low Pgp activityasavicibeusan■ рЕЯЄ∙OhлС+'│┘0ЁРШ(4DP\p АМ м ╕ ─╨╪рштИLow levels of residual disease in CML are associated with low molecular level of oncogene BCR-ABL chimeric genes and low Pgp activityasavic Normal.dotibeusan2Microsoft Office Word@F├#@^<8%Х╦@^<8%Х╦^■ ╒═╒Ь.УЧ+,∙о0М hpШаи░ ╕└╚╨ ╪ jт Institute of Immunology, inc. x' ЖLow levels of residual disease in CML are associated with low molecular level of oncogene BCR-ABL chimeric genes and low Pgp activity Naslov ■   ■   ■    !"#$%&■   ¤   )■   ■   ■                                                                                                                                                                                                                                                                                                                                                   Root Entry         └F└┌cB%Х╦+А1Table        WordDocument        8SummaryInformation(    DocumentSummaryInformation8            CompObj            s                        ■                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           ■       └F!Microsoft Office Wordov dokument MSWordDocWord.Document.8Ї9▓q