Mutant ASXL1 induces age-related expansion of phenotypic hematopoietic stem cells through activation of Akt/mTOR pathway

Mutant ASXL1 induces age-related expansion of phenotypic hematopoietic stem cells through activation of Akt/mTOR pathway

ASXL1 mutations are frequently found in age-related clonal haemaotopoiesis (CH), but how they drive CH is unclear. Here the authors show that expression of C-terminal truncated ASXL1 in haematopoietic stem cells (HSCs) leads to Akt de-ubiquitination, activated Akt/mTOR signaling, and aberrant HSC pr...

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Autores principales: Takeshi Fujino, Susumu Goyama, Yuki Sugiura, Daichi Inoue, Shuhei Asada, Satoshi Yamasaki, Akiko Matsumoto, Kiyoshi Yamaguchi, Yumiko Isobe, Akiho Tsuchiya, Shiori Shikata, Naru Sato, Hironobu Morinaga, Tomofusa Fukuyama, Yosuke Tanaka, Tsuyoshi Fukushima, Reina Takeda, Keita Yamamoto, Hiroaki Honda, Emi K. Nishimura, Yoichi Furukawa, Tatsuhiro Shibata, Omar Abdel-Wahab, Makoto Suematsu, Toshio Kitamura
Formato: article
Lenguaje:EN
Publicado: Nature Portfolio 2021
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Acceso en línea:https://doaj.org/article/5a4339b6caee4c1d9bbb984e54dddbf0
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Sumario:ASXL1 mutations are frequently found in age-related clonal haemaotopoiesis (CH), but how they drive CH is unclear. Here the authors show that expression of C-terminal truncated ASXL1 in haematopoietic stem cells (HSCs) leads to Akt de-ubiquitination, activated Akt/mTOR signaling, and aberrant HSC proliferation.

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