Mutant ASXL1 cooperates with BAP1 to promote myeloid leukaemogenesis

• Published in: Nature communications Vol. 9; no. 1; pp. 2733 - 18
• Main Authors: Asada, Shuhei, Goyama, Susumu, Inoue, Daichi, Shikata, Shiori, Takeda, Reina, Fukushima, Tsuyoshi, Yonezawa, Taishi, Fujino, Takeshi, Hayashi, Yasutaka, Kawabata, Kimihito Cojin, Fukuyama, Tomofusa, Tanaka, Yosuke, Yokoyama, Akihiko, Yamazaki, Satoshi, Kozuka-Hata, Hiroko, Oyama, Masaaki, Kojima, Shinya, Kawazu, Masahito, Mano, Hiroyuki, Kitamura, Toshio
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 16.07.2018; Nature Publishing Group; Nature Portfolio
• Subjects: 13/31; 14/19; 38/109; 38/91; 45/15; 49/88; 631/208/176; 631/67/1990/283; 64/60; 82/29; 82/58; Animals; Bone Marrow - metabolism; Bone Marrow - pathology; Bone Marrow Transplantation; Carcinogenesis - genetics; Carcinogenesis - metabolism; Carcinogenesis - pathology; Catalysis; Cells (biology); Core Binding Factor Alpha 2 Subunit - genetics; Core Binding Factor Alpha 2 Subunit - metabolism; CRISPR-Cas Systems; Female; Gene Editing; Gene expression; Gene Expression Regulation, Leukemic; HEK293 Cells; HeLa Cells; Homeodomain Proteins - genetics; Homeodomain Proteins - metabolism; HOXA gene; Humanities and Social Sciences; Humans; Interferon Regulatory Factors - genetics; Interferon Regulatory Factors - metabolism; Leukemia; Leukemia, Myeloid - genetics; Leukemia, Myeloid - metabolism; Leukemia, Myeloid - mortality; Leukemia, Myeloid - pathology; Male; Mice; Mice, Inbred C57BL; multidisciplinary; Mutation; Myeloid leukemia; Neoplasia; Neoplasms; Progenitor cells; Repressor Proteins - genetics; Repressor Proteins - metabolism; Runx1 protein; RUNX1 Translocation Partner 1 Protein - genetics; RUNX1 Translocation Partner 1 Protein - metabolism; Science; Science (multidisciplinary); Signal Transduction; Stem cells; Survival Analysis; Tumor suppressor genes; Tumor Suppressor Proteins - genetics; Tumor Suppressor Proteins - metabolism; Tumors; Ubiquitin Thiolesterase - genetics; Ubiquitin Thiolesterase - metabolism; Ubiquitination; Whole-Body Irradiation

ASXL1 mutations occur frequently in myeloid neoplasms and are associated with poor prognosis. However, the mechanisms by which mutant ASXL1 induces leukaemogenesis remain unclear. In this study, we report mutually reinforcing effects between a C-terminally truncated form of mutant ASXL1 (ASXL1-MT) a...