News Releases & Research Results Anomalous localization of KIT tyrosine kinase in acute myeloid leukemia ―Inhibition of KIT signaling in the Golgi apparatus by M-COPA, an inhibitor of intracellular trafficking―

News Releases & Research Results

Outline

Results of R&D by a collaborative research group of Visiting Associate Professor Yuuki Obata of the Research Institute for Science and Technology, Tokyo University of Science, Professor Isamu Shiina of the Department of Applied Chemistry, Faculty of Science, Tokyo University of Science, Appointed Professor Ryo Abe of the Strategic Innovation and Research Center, Teikyo University, Director Toshiro Nishida of the National Cancer Center Hospital, Division Chief Koji Okamoto of the National Cancer Center Research Institute, and others.

Key points of the study results

  • Study revealed that if "KIT" mutations (*1) are present in acute myeloid leukemia (*2), growth signaling occurs on the Golgi apparatus (*3) and not in the plasma membrane as previously thought.
    *1: A gene found in feline sarcoma virus. KIT is activated when bound to a growth factor in the plasma membrane of hematopoietic stem cells, etc., and promotes cell differentiation and proliferation.
    *2: Cancer that grows by uncontrollable hematopoietic progenitor cells. It occurs in 3,000 to 4,000 individuals per year in Japan.
    *3: An organelle that plays a "distribution center" role in cells.
  • Furthermore, it was found that M-COPA (2-methylcoprophilinamide), the inhibitor of intracellular trafficking, blocks the KIT migration to the Golgi apparatus in acute myeloid leukemia, and suppresses the signals that can lead to unlimited proliferation.
  • The results showed that M-COPA and its derivatives, which are a potential therapeutic agent for gastrointestinal stromal tumors, could also treat acute myeloid leukemia.

This R&D was conducted with the support of Project for Cancer Research and Therapeutic Evolution (P-CREATE) by AMED.

The results of R&D were published on September 10 in Cell Communication & Signaling.

Article

Obata Y., et al. N822K- or V560G-mutated KIT activation preferentially occurs in lipid rafts of the Golgi apparatus in leukemia cells, Cell Communication & Signaling
DOI:10.1186/s12964-019-0426-3

09/19/19

Last updated 09/19/19