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Activation of NOTCH signaling impedes cell proliferation and survival in acute megakaryoblastic leukemia.
Ong, Kelly Ooi Kee; Mok, Michelle Meng Huang; Niibori-Nambu, Akiko; Du, Linsen; Yanagida, Masatoshi; Wang, Chelsia Qiuxia; Bahirvani, Avinash Govind; Chin, Desmond Wai Loon; Koh, Cai Ping; Ng, King Pan; Yamashita, Namiko; Jacob, Bindya; Yokomizo, Tomomasa; Takizawa, Hitoshi; Matsumura, Takayoshi; Suda, Toshio; Lau, Jie-Ying Amelia; Tan, Tuan Zea; Mori, Seiichi; Yang, Henry; Iwasaki, Masayuki; Minami, Takashi; Asou, Norio; Sun, Qiao-Yang; Ding, Ling-Wen; Koeffler, H Phillip; Tenen, Daniel G; Shimizu, Ritsuko; Yamamoto, Masayuki; Ito, Yoshiaki; Kham, Shirley Kow Yin; Yeoh, Allen Eng-Juh; Chng, Wee Joo; Osato, Motomi.
Afiliação
  • Ong KOK; Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
  • Mok MMH; Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
  • Niibori-Nambu A; Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
  • Du L; Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
  • Yanagida M; Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
  • Wang CQ; Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore; Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore; Bioprocessing Technology Institute, A*STAR, Singapore.
  • Bahirvani AG; Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
  • Chin DWL; Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
  • Koh CP; Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
  • Ng KP; Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
  • Yamashita N; Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
  • Jacob B; Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore; Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
  • Yokomizo T; Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore; International Research Center for Medical Sciences, Kumamoto University, Japan.
  • Takizawa H; International Research Center for Medical Sciences, Kumamoto University, Japan.
  • Matsumura T; Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
  • Suda T; Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
  • Lau JA; Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
  • Tan TZ; Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
  • Mori S; Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
  • Yang H; Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
  • Iwasaki M; Institute of Laboratory Animals, Tokyo Women's Medical University, Japan.
  • Minami T; Center for Animal Resources and Development, Kumamoto University, Japan.
  • Asou N; International Medical Center, Saitama Medical University, Japan.
  • Sun QY; Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
  • Ding LW; Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
  • Koeffler HP; Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
  • Tenen DG; Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
  • Shimizu R; Graduate School of Medicine, Tohoku University, Japan.
  • Yamamoto M; Graduate School of Medicine, Tohoku University, Japan.
  • Ito Y; Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore; Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
  • Kham SKY; Department of Paediatrics, National University of Singapore, Singapore, Singapore.
  • Yeoh AE; Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore; Department of Paediatrics, National University of Singapore, Singapore, Singapore. Electronic address: allen_yeoh@nuhs.edu.sg.
  • Chng WJ; Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore; Department of Haematology-Oncology, National University Cancer Institute, Singapore, National University Health System, Singapore, Singapore; Department of Medicine, Yong Loo Lin School of Medicine, Nation
  • Osato M; Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore; Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore; International Research Center for Medical Sciences, Kumamoto University, Japan; Departme
Exp Hematol ; 137: 104255, 2024 Sep.
Article em En | MEDLINE | ID: mdl-38876252
ABSTRACT
The genetic lesions that drive acute megakaryoblastic leukemia (AMKL) have not been fully elucidated. To search for genetic alterations in AMKL, we performed targeted deep sequencing in 34 AMKL patient samples and 8 AMKL cell lines and detected frequent genetic mutations in the NOTCH pathway in addition to previously reported alterations in GATA-1 and the JAK-STAT pathway. Pharmacological and genetic NOTCH activation, but not inhibition, significantly suppressed AMKL cell proliferation in both in vitro and in vivo assays employing a patient-derived xenograft model. These results suggest that NOTCH inactivation underlies AMKL leukemogenesis. and NOTCH activation holds the potential for therapeutic application in AMKL.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Transdução de Sinais / Leucemia Megacarioblástica Aguda / Proliferação de Células / Receptores Notch Limite: Animals / Female / Humans / Male Idioma: En Ano de publicação: 2024 Tipo de documento: Article
Texto completo
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Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Transdução de Sinais / Leucemia Megacarioblástica Aguda / Proliferação de Células / Receptores Notch Limite: Animals / Female / Humans / Male Idioma: En Ano de publicação: 2024 Tipo de documento: Article