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Analiza mutacij v kinazni domeni proteina BCR-ABL1 pri bolnikih s kronično mieloično levkemijo in z nezadostnim odgovorom na zdravljenje z zaviralcem tirozinske kinaze = BCR-ABL1 kinase domain mutation analysis in chronic myeloid leukaemia patients with suboptimal response to tyrosine kinase inhibitorsPajič, Tadej ...Izhodišča: Pri bolnikih s kronično mieloično levkemijo (KML) lahko pridobljenemutacije v kinazni domeni proteina BCR-ABL1 prispevajo k neučinkovitemu zdravljenju z zaviralcem tirozinske kinase (TK). ... Z našim delom želimo napraviti mutacijsko analizo v skupini bolnikov s KML, ki so jih zdravili z zaviralcem TK in ki niso dosegli glavnega molekularnega odgovora (MolO) v najmanj 18 mesecih ali pa so ga izgubili. Metode: V raziskavo smo vključili 9 bolnikov s KML (7 žensk, 2 moška). Iz levkocitov periferne krvi smo osamili celotno RNA in pripravili komplementarno DNA (cDNA) z reverzno transkripcijo. V preurejenem alelu BCR-ABL1 smo z načinom vgnezdene verižne reakcije s polimerazo (PCR) pomnožili celotni odsek kinazne domene ABL1. Nukelotidno zaporedje pridelka PCR smo določili s sekvenciranjem, ki smo ga izvedli na napravi ABI Prism 310. Dobljeno zaporedje smo primerjali z nukelotidnim zaporedjem divjega tipa gena ABL1. Mutacijo T315I smo ugotavljalitudi z občutljivejšim načinom, z alelno specifičnim PCR. Mutacija T315I je odporna tako na imatinib, nilotinib in dasatinib. Rezultati: S sekvenciranjem in ASO-PCR smo pri enem od 9 bolnikov s KML dokazali prisotnostmutacije T315I. Pri drugem bolniku smo s sekvenciranjem ugotovili tiho mutacijo p.Glu499Glu. Pri ostalih bolnikih mutacij nismo ugotovili. Zaključki: Mutacije so najverjetneje redke pri bolnikih s KML, ki niso dosegliglavnega MolO najmanj po 18 mesecih ali so ga izgubili. Ugotovitev mutacije T315I, odporne na zaviralce TK (imatinib, nilotinib, dasatinib), v naši raziskavi kaže, da je analizo mutacij v BCR-ABL1 smiselno opraviti pri tej skupini bolnikov. Ugotovljena tiha mutacija, pri kateri ni prišlo do zamenjave aminokisline, je zavedena v glavnih podatkovnih bazah polimorfizmov posameznih nukleotidov (SNP, rs2227985). Vpliv polimorfizma na odpornost za zdravljenje z zaviralcem TK ni pojasnjena.Source: 4. kongres hematologov in transfuziologov Slovenije (Letn. 81, suppl., nov. 2012, str. II-174-II-179)Type of material - conference contributionPublish date - 2012Language - slovenianCOBISS.SI-ID - 698028
source: 4. kongres hematologov in transfuziologov Slovenije (Letn. 81, suppl., nov. 2012, str. II-174-II-179)
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Database name | Field | Year |
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Pajič, Tadej | 23818 |
Lamovšek, Nejc | 35674 |
Fink, Martina | 18992 |
Preložnik Zupan, Irena, medicina | 23126 |
Černelč, Peter | 07012 |
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