Da li farmakogenetika ima uticaj na ishod lečenja odraslih pacijenata sa akutnom mijeloidnom leukemijom lečenih primenom citarabina i antraciklina? Srpsko iskustvo

  • Zlatko Pravdić Clinic of Hematology, University Clinical Centre of Serbia, Belgrade
  • Marijana Virijević Clinic of Hematology, University Clinical Centre of Serbia, Belgrade; Faculty of Medicine, University of Belgrade, Belgrade, Serbia
  • Mirjana Mitrović Clinic of Hematology, University Clinical Centre of Serbia, Belgrade; Faculty of Medicine, University of Belgrade, Belgrade, Serbia
  • Nikola Pantić Clinic of Hematology, University Clinical Centre of Serbia, Belgrade
  • Nikica Sabljić Clinic of Hematology, University Clinical Centre of Serbia, Belgrade
  • Đorđe Pavlović Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia
  • Irena Marjanović
  • Zoran Bukumirić Institute of Medical Statistics and Informatics, Faculty of Medicine, University of Belgrade, Belgrade, Serbia
  • Ana Vidović Clinic of Hematology, University Clinical Centre of Serbia, Belgrade; Faculty of Medicine, University of Belgrade, Belgrade, Serbia
  • Ljubomir Jaković Clinic of Hematology, University Clinical Centre of Serbia, Belgrade
  • Sonja Pavlović Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia
  • Nada Suvajdžić Clinic of Hematology, University Clinical Centre of Serbia, Belgrade; Faculty of Medicine, University of Belgrade, Belgrade, Serbia
  • Vladimir Gasic Institute of Molecular Genetics and Genetic Engineering
DOI: https://doi.org/10.5937/jomb0-47459
Ključne reči: AML, Antraciklini, Citarabin, Farmakogenetičke varijante

Sažetak


Uvod. Indukciona terapija zasnovana na citarabinu i antraciklinu standard je lečenja novodijagnostikovanih odraslih pacijenata sa akutnom mijeloidnom leukemijom (AML). Ishodi lečenja među obolelima od AML značajno se razlikuju. Ove razlike bi se delimično mogle objasniti genetičkim varijabilitetom metaboličkih puteva citarabina i antraciklina. Cilj ovog istraživanja bilo je ispitivanje uticaja varijanti u farmakogenima SLC29A1, DCK, ABCB1, GSTM1 i GSTT1, kao i laboratorijskih i parametara vezanih za AML na ishode lečenja odraslih bolesnika sa AML.    

Metode. Ukupno 100 bolesnika sa AML je uključeno u studiju. Farmakogenetičke varijante SLC29A1 rs9394992, DCK rs12648166, ABCB1 rs2032582 i delecije gena GSTM1 i GSTT1 određivane su metodologijom zasnovanom na PCR-u, analizom fragmenata i direktnim sekvenciranjem. Korišćene su metode deskriptivne i analitičke statistike. Analiza preživljavanja je sprovedena prema Kaplan-Majerovom metodu upotrebom Log-Rank testa.

Rezultati. Ovo je prva farmakogenetička studija odraslih bolesnika sa AML u srpskoj populaciji. Varijante u genima SLC29A1, DCK, ABCB1, GSTT1 i GSTM1 nisu uticale na ishode lečenja u našoj kohorti obolelih od AML, samostalno ili u međusobnim kombinacijama. Međutim, postizanje kompletne remisije bolesti istaklo se kao nezavisni prediktor ishoda lečenja.

Zaključak. Prilikom farmakogenetičkih istraživanja neophodno je razmotriti jedinstveni genetički profil ispitivane populacije. Kako su farmakogenetički podaci o AML u evropskim populacijama oskudni, naši rezultati doprinose proširenju saznanja u ovoj oblasti i ukazuju na značaj primena tehnika sekvenciranja nove generacije u cilju otkrivanja posebnih farmakogenetičkih markera kod obolelih od AML u evropskim populacijama.

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Objavljeno
2024/04/26
Broj časopisa
Vol. 43 Br. 4 (2024): Journal of Medical Biochemistry
Rubrika
Original paper

Sva prava zadržana (c) 2024 Zlatko Pravdic, Marijana Virijević, Mirjana Mitrović, Nikola Pantić, Nikica Sabljić, Đorđe Pavlović, Irena Marjanović, Zoran Bukumirić, Ana Vidović, Ljubomir Jaković, Sonja Pavlović, Nada Suvajdžić, Vladimir Gasic

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