Důležitá role STAT3 v biologii chronické lymfocytární leukemie

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Autori: M. Boudny; M. Trbusek
Pôsobisko autorov: Department of Internal Medicine, Hematology and Oncology, Faculty of Medicine, Masaryk University and University Hospital Brno
Vyšlo v časopise: Klin Onkol 2020; 33(1): 32-38
Kategória: Review
doi: https://doi.org/10.14735/amko202032

Súhrn

Východiska: Proteiny STAT (signal transducer and activator of transcription) jsou cytoplazmatické transkripční faktory, které přenášejí signál cytokinů, hormonů a růstových faktorů. Proteiny STAT kontrolují základní buněčné procesy vč. přežití, proliferace a diferenciace. Nadměrná aktivace proteinů STAT může přispět k transformaci buněk a vzniku leukemie. Okolo 70 % všech solidních a hematologických nádorů vykazuje aberantní expresi a/nebo aktivaci STAT3, což dokumentuje zásadní roli STAT3 v tumorigenezi. Aberantní aktivace STAT3 byla popsána u několika solidních nádorů a hematologických malignit. Důležité je, že konstitutivní aktivace proteinů STAT byla detekována u několika typů leukemie vč. akutní myeloidní leukemie, akutní promyelocytární leukemie, akutní lymfoblastické leukemie, chronické myeloidní leukemie a chronické lymfocytární leukemie (CLL). Konstitutivně aktivovaný STAT3 hraje důležitou roli v biologii CLL. Buňky CLL jsou konstitutivně fosforylované na S727 a acetylované na K685, navíc může dojít i k fosforylaci na Y705. Exprese mediátorové RNA STAT3 je výrazně vyšší v buňkách CLL ve srovnání se zdravými B lymfocyty. Zajímavé je, že inhibice STAT3 byla popsána jako důležitý vedlejší produkt léčby ibrutinibem u pacientů s CLL.

Cíl: Účelem tohoto přehledu je popsat důsledky deregulace STAT3 u buněk CLL. V práci jsou popsány procesy ovlivněné nadměrnou aktivací STAT3 jako proliferace, apoptóza, signalizace BCR (B cell receptor), sekrece cytokinů, regulace kontrolních bodů imunitního systému, regulace mikroRNA, metabolizmus mastných kyselin a elektronový transportní řetězec v mitochondriích.

Práce byla podpořena projektem FNBr 65269705 – koncepční rozvoj výzkumné organizace a projektem MUNI/A/1105/2018.

Autoři deklarují, že v souvislosti s předmětem studie nemají žádné komerční zájmy.

Redakční rada potvrzuje, že rukopis práce splnil ICMJE kritéria pro publikace zasílané do biomedicínských č asopisů.

Obdrženo: 11. 9. 2019

Přijato: 6. 11. 2019

Klíčová slova:

STAT3 – STAT – chronická lymfocytární leukemie – terapie – mikroprostředí – ibrutinib – konstitutivní aktivace – leukemie

Zdroje

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