127 KB12 KB192920262004Jakšić, BranimirKušec, RajkoMarušić-Vršalović, MaruškaMingo, HrvojeOstojić, SlobodankaVranić-Bobetić, Tanjastr. I-5-I-7ISSN:1318-0347COBISSID_HOST:17634009URN:URN:NBN:SI:doc-HG9OJ0EQenSlovensko zdravniško društvoZdravniški vestnikEksoniExonsFenotipGenes, FmsGeneticsGeni fmsKariotip, določanjeKaryotypingLeukemia, Myelocytic, AcuteLevkemija mielocitna, akutnaPhenotypePolimerazna, verižna reakcijaPolymerase Chain ReactionPreživetje, analizaPrognosisPrognozaSurvival AnalysisFMS-like tyrosine kinase (FLT3) gene ITD mutation in acute myeloid leukemia| Mutacija gena FLT3 pri akutni mieloblastni levkemiji|Background. FLT3 is a class III receptor tyrosine kinase expressed in normal stem cells and blasts of myeloid leukemia. Internal tandem duplication (ITD) of the FLT3 gene affecting the exons 14 and 15 leads to ligand-independent FLT3 dimerization and constitutive activation. This stimulates proliferation and induces inhibition of apoptosis which contributes to leukemogenesis. We have screened a panel of acute myeloid leukemia (AML) patients for the occurrence of FLT3/ITD mutation and correlated this mutation to patients' survival and basic hematological parameters. Methods. RT-PCR for ITD in exons 14 and 15 of FLT3 gene was done on bone marrow samples of 67 AML patients at diagnosis. Results. There was a 16.4% incidence of FLT3/ITD mutation in the cohort of examined patients. By cytognetic subgroups there were 2/6 t(15; 17) and 1 of 4 t(8;21) positive patients. The rest had normal and 2 had complex karyotype. Majority were of FAB M2 or M4 phenotype. For a subset of patients taken into comparative survival analysis there was a clear disadvantage for FLT3/ITD patients. No difference was found for basic hematological parameters between two groups. Conclusions. As it is evident today that FLT3/ITD is the single most common genetic abnormality in AML that also presents unfavorable clinical prognostic marker, it should be included in molecular diagnostic testing of acute myeloid leukemiaIzhodišča. FLT3 je receptor razreda III za tirozin kinazo. Nahaja se v normalnih matičnih celicah in levkemičnih celicah pri aktuni mieloblastni levkemiji (AML). Notranja tandemska podvojitev (ITD) gena FLT3 na eksonih 14 in 15 vodi do nastanka neodvisnih dimerov in aktivacije s posledično proliferacijo in inhibicijo apoptoze, kar v končni fazi vodi do levkemogeneze.Pregledali smo vzorce serije bolnikov z AMI za prisotnost mutacije FLT3/ITD in ugotavljali morebitno povezavo med prisotnostjo mutacije s klinično sliko in potekom bolezni. Metode. Z metodo verižne reakcije s polimerazo v realnem času (RT-PCR) smo preiskali 67 vzorcev kostnega mozga bolnikov z AML za prisotnost ITD na eksonih 14 in 15 gena FLT3. Rezultati. V skupini pregledanih vzorcev je bila incidenca FLT3/ITD mutacije 16,4%. Mutacijo smo ugotovili pri 2 do 6 bolnikih s translokacijo t (15; 17), pri 1 od 4 s translokacijo kariotip. Večina je imela fenotip AML M2 in M4 po FAB razdelitvi. Pri bolnikih z mutacijo je bolezen kazala slabši potek in prežive je, ni pa bilo nobenih razlik v osnovnih hematoloških parametrih med skupinamiz mutacijo in brez. Zaključki. Znano je, da je mutacija FIT3/ITD najpogostejša samostojna mutacija pri bolnikih z AML in predstavlja neugoden dejavnik napovedi poteka bolezni. Zaradi tega bi morali to preiskavo vključitiv redno molekularno diagnostično preiskovanje bolnikov z AMLTEXTznanstveno časopisjejournalsSlovenian National E-content AggregatorNational and University Library of SloveniaSlovensko zdravniško društvo