Izohromozom der(17)(q10)t(15;17) u akutnoj promijelocitnoj leukemiji rezultira dodatnom kopijom RARA-PML i gubitkom p53 gena: prikaz dva slučaja i pregled literature

  • Vesna Djordjević Clinical Center of Serbia, Clinic of Hematology, Belgrade, Serbia
  • Marija Denčić Fekete Clinical Center of Serbia, Clinic of Hematology, Belgrade, Serbia
  • Jelica Jovanović Clinical Center of Serbia, Clinic of Hematology, Belgrade, Serbia
  • Marijana Virijević Clinical Center of Serbia, Clinic of Hematology, Belgrade, Serbia; University of Belgrade, Faculty of Medicine, Belgrade, Serbia
  • Nada Kraguljac Kurtović Clinical Center of Serbia, Clinic of Hematology, Belgrade, Serbia
  • Ljubomir Jaković Clinical Center of Serbia, Clinic of Hematology, Belgrade, Serbia; University of Belgrade, Faculty of Medicine, Belgrade, Serbia
  • Andrija Bogdanović Clinical Center of Serbia, Clinic of Hematology, Belgrade, Serbia; University of Belgrade, Faculty of Medicine, Belgrade, Serbia
DOI: https://doi.org/10.2298/VSP170824174D
Ključne reči: leukemija, mijelocitna, akutna, hromosomi, aberacije, faktori transkripcije, hibridizacija in situ, fluorescentna, translokacija (genetika), geni p53, mortalitet, retinoična kiselina, receptor alfa

Sažetak


Apstrakt

 

Uvod. Izohromozom dugog kraka derivata hromozoma 17, koji potiče od translokacije t(15;17) [ider(17)(q10)t(15;17) ili ider(17q)] u akutnoj promijelocitnoj leukemiji (APL), je retka hromozomska aberacija, povezana sa lošom prognozom. Prikaz bolesnika. Prikazali smo dva bolesnika čiji su klinički i laboratorijski podaci ukazivali na dijagnozu APL. Citogenetička analiza ćelija kostne srži oba bolesnika, pokazala je mozaičan kariotip sa ider(17q); reverzna transkripcija lančane reakcije polimeraze (RT-PCR) bila je pozitivna za dugu (L) izoformu fuzionog PML-RARA (retinoinska kiselina receptor alfa) transkripta. Analiza, fluorescentna in situ hibridizacija (FISH) sa DNA probama za PML gen na 15q24.1 i RARA gen na 17q21.2, potvrdila je prisustvo dodatne kopije RARA-PML fuzionog gena ili ider(17q). Pored toga, FISH analiza sa DNA probom za p53 gen na 17p13.1 potvrdila je gubitak jedne kopije univerzalnog tumor supresor gena p53 kod oba bolesnika. Zaključak. Kod oba bolesnika registrovana je dominacija patološkog klona sa ider(17q) u odnosu na klon sa klasičnom translokacijom t(15;17) i/ili klon sa normalnim kariotipom, što ukazuje na mogućnost da duplicirani der(17q) obezbeđuje proliferativnu prednost patološkom ćelijskom klonu. Nastankom ove aberacije dolazi i do gubitaka jedne kopije univerzalnog tumor supresor gena p53. To je dodatni, onkogeni događaj u neoplastičnom procesu i loš prognostički parameter za bolesnike sa APL, jer se time povećava efekat proliferativne prednosti leukemijskih ćelija. Iako klinički i prognostički značaj aberacije ider(17q) i dalje ostaje nejasan, kroz primer dva naša bolesnika možemo zaključiti da se isključivo kombinovanjem citogenetičkih i molekularno-genetičkih analiza mogu donekle obezbediti uslovi za razotkrivanje detalja o ovoj kompleksnoj i retkoj hromozomskoj abnormalnosti.

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Objavljeno
2021/04/21
Broj časopisa
Vol. 76 Br. 9 (2019): Vojnosanit Pregl
Rubrika
Prikaz bolesnika