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Alteration of phosphatidylinositol 3-kinase cascade in the multilobulated nuclear formation of adult T cell leukemia/lymphoma (ATLL)

-i: Fukuda, R., Hayashi, A., Utsunomiya, A., Nukada, Y., Fukui, R., Itoh, K., Tezuka, K., Ohashi, K., Mizuno, K., Sakamoto, M. ORCID: https://orcid.org/0000-0001-6447-406X, Hamanoue, M. and Tsuji, T. (2005) Alteration of phosphatidylinositol 3-kinase cascade in the multilobulated nuclear formation of adult T cell leukemia/lymphoma (ATLL). Proceedings of the National Academy of Sciences of the United States of America, 102 (42). pp. 15213-15218. ISSN 0027-8424

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To link to this item DOI: 10.1073/pnas.0507184102

Abstract/Summary

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 phosphatidylinositol 3-kinase (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 down-regulation 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. Thus, our results suggest that alteration of PI3-kinase signaling cascades, as a result of the down-regulation of inositol phosphatases, induces ATLL-type multilobulated nuclear formation and is also associated with the cellular proliferation of malignant T cell leukemias/lymphomas.

Item Type:Article
Refereed:Yes
Divisions:Life Sciences > School of Biological Sciences > Ecology and Evolutionary Biology
ID Code:117255
Publisher:National Academy of Sciences

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