Prognostički značaj mutacija u genima za izocitrat dehidrogenazu 1 (IDH1) i izocitrat dehidrogenazu 2 (IDH2) u akutnoj mijeloidnoj leukemiji sa normalnim kariotipom
Prognostic impact of isocitrate dehydrogenase 1 (IDH1) and isocitrate dehydrogenase 2 (IDH2) mutations on outcome in acute myeloid leukemia with normal karyotype
Abstract
Mutacije u genima za izocitrat dehidrogenazu 1 i 2 (IDH1 i IDH2) su česte rekurentne
molekularne promene kod akutne mijeloidne leukemije sa normalnim kariotipom (AMLNK).
Uticaj IDH mutacija na kliničke karakteristike i ishod lečenja kod AML-NK su u
velikoj meri istražene, ali samo nekoliko studija je pratilo ove mutacije u toku bolesti.
Ciljevi: 1) Utvrđivanje učestalosti prisustva IDH1 i IDH2 mutacija kod bolesnika sa AMLNK;
2) Utvrđivanje uticaja prisustva IDH1 i IDH2 mutacija na učestalost i dužinu remisije,
ukupno preživljavanje i povezanosti IDH1 i IDH2 mutacija i drugih prognostičkih markera:
parametri krvne slike, biohemijski parametri, citološki tip bolesti, imunofenotipska i
molekularno-genetska obeležja (FLT3 i NPM1 mutacije); 3) Utvrđivanje stabilnosti IDH1 i
IDH2 mutacija u toku bolesti poređenjem uzoraka na početku bolesti sa uzorcima u toku
kompletne remisije (KR), odnosno u recidivu bolesti.
Materijal i metodologija istraživanja: Uzorci od 110 starijih de novo AML-NK bol...
Mutations in the isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) genes are
frequent recurrent molecular lesions in acute myeloid leukemia with normal karyotype
(AML-NK). The effects of IDH mutations on clinical features and treatment outcome in
AML-NK have been widely investigated, but only a few studies monitored these mutations
during follow-up.
Aim: 1) To determine the frequency of presence of IDH1 and IDH2 mutations in patients
with AML-NK; 2) To determine the effect of the presence of IDH1 and IDH2 mutations on
duration of remission, overall survival and the association IDH1 and IDH2 mutations and
other prognostic markers: blood parameters, the biochemical parameters, cytological disease
type, immunophenotypic and molecular-genetic characteristics (FLT3 and NPM1 mutations);
3) To determine the stability IDH1 and IDH2 mutations in the course of the disease by
comparing the samples at the start of the disease with samples during complete remission
(CR), and in a relapse of the dise...