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  • 1 Semmelweis Egyetem, 1085 Budapest, Üllői út 26.
  • 2 Dél-pesti Centrumkórház, Budapest
  • 3 Semmelweis Egyetem, Budapest
Open access

Absztrakt:

A krónikus limfocitás leukémia a nyugati világban leggyakrabban előforduló felnőttkori leukémiatípus, mely heterogén klinikai lefolyással és változatos genetikai háttérrel társul. A széles körben alkalmazott kemo-immunoterápiák mellett az elmúlt években új, célzott kezeléseket biztosító kis molekulájú gyógyszerek váltak elérhetővé, mint a kinázgátló ibrutinib, acalabrutinib és idelalisib, valamint a BCL2 antagonista venetoclax. Jelenleg hazánkban a krónikus limfocitás leukémia terápiáját forradalmasító, korszerű kezelések közül az ibrutinib monoterápia nemcsak relabáló vagy refrakter betegeknél, hanem rossz prognózisú, TP53-defektust hordozó betegeknél első vonalban is alkalmazható. A látványos klinikai sikerek ellenére a betegek egy részében rezisztencia alakul ki ibrutinibkezelés mellett, melynek hátterében álló genetikai változásokhoz és molekuláris mechanizmusokhoz kapcsolódóan egyre több adat áll rendelkezésre a nemzetközi irodalomban. Közleményünkben ismertetjük a B-sejt receptor jelátviteli útvonalnak a krónikus limfocitás leukémia patogenezisében betöltött szerepét, mely egyúttal az ibrutinibkezelés célpontjaként is szolgál. Továbbá bemutatjuk az ibrutinibterápia hatásmechanizmusát és sajátosságait, valamint a kezelés során megjelenő, klinikai rezisztenciát kísérő genetikai változásokat. Végül áttekintjük a terápiás rezisztencia molekuláris módszerekkel való monitorozásának és korai kimutatásának lehetőségeit és korlátait, valamint a rezisztencia megjelenését követően alkalmazható kezelési lehetőségeket.

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