A research group headed by Takashi Tsuji of the Tokyo University of Science's Tissue Engineering Research Center identified mechanisms behind outbreaks of adult T-cell leukemia. This research was pursued in collaboration with Yoshi Utsunomiya from Foundation Jiaikai Imamura Bun-in Hospital and Katsuhiko Ito from Kyoto University and other researchers. The results of this research are expected to lead to the development of new treatments for adult T-cell leukemia.
Adult T-cell leukemia/lymphoma (ATLL) has been characterized as one of the most aggressive human neoplasias and its incidence is thought to be caused by both genetic and epigenetic alterations to the host cellular genes of T-cells infected with human T-cell leukemia virus type I (HTLV-I). A multilobulated nuclear appearance is an important diagnostic marker of ATLL and we have now identified that the molecular mechanisms underlying these formations occur through microtubule rearrangement via PI3-kinase activation by AILIM/ICOS-signaling.
We also show that PTEN and/or SHIP-1, which are PIP3 inositol phosphatases that inhibit the activation of downstream effectors of the PI3-kinase cascade, are disrupted in both ATLL neoplasias and in multilobulated nuclei-forming Jurkat cells. This downregulation of PTEN was found to be essential for the formation of ATLL-type nuclear lobules. Furthermore, PI3-kinase and PTEN activities were observed to be closely associated with cellular proliferation. Our results thus suggest that alteration of PI3-kinase signaling cascades, as a result of the downregulation of inositol phosphatases, induces ATLL-type multilobulated nuclear formation and is also associated with the cellular proliferation of malignant T-cell leukemias/lymphomas.
Takashi Tsuji is Assistant Professor at the Department of Biological Science and Technology, Faculty of Industrial Science and Technology, Tokyo University of Science
Yoshi Utsunomiya is Director of the Foundation Jiaikai Imamura Bun-in Hospital in Kagoshima City
Katsuhiko Ito is a Lecturer in Graduate School of Medicine, Kyoto University
Yasuhiro Tomooka is Director of the Tokyo University of Science's Tissue Engineering Research Center, which is a base for the Academic Frontier Project for Japan's Ministry of Education, Culture, Sports, Science, and Technology.
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