ENAGenomicsMolecular Pathology, Oita university, Faculty of Medicinehttps://www.ebi.ac.uk/ena/browser/view/PRJNA708289Homo sapiensAdult T-cell leukaemia-lymphoma (ATL) is a highly chemoresistant malignancy of peripheral T lymphocytes caused by human T-lymphotropic virus type I (HTLV-1). ATL cells constitutively activate anti-apoptotic signals through nuclear factor kappaB (NF-κB)-mediated gene expression. The molecular chaperon heat shock protein 90 (HSP90) plays a crucial role on NF-κB-mediated anti-apoptotic activity in ATL cells and HSP90 inhibitors, such as 17-DMAG and NVP-AUY922, have demonstrated their anti-ATL activities. A novel class of orally active inhibitors of cytosolic HSP90α and β, pimitespib, demonstrated its highly selective anti-ATL cell effects both ex-vivo and in vivo preclinical models. Ten ATL-related cell lines achieved their IC50 below 0.5µM dose of TAS-116 while CD4 lymphocytes derived from healthy donors were less harmed than ATL cells. TAS-116 efficiently induces Tax-degradation and IκB-α accumulation to Tax-positive cell-lines. DNA microarray profiling followed by a variety of pathway analysis revealed that TAS-116 down-regulated NF-κB activating pathways in Tax-positive cells and cell cycle promoting pathways in Tax-negative cells and induces anti-ATL effect. Oral administration of TAS-116 to ATL-cell xenograft model mice also demonstrated the growth inhibitory effects against tumor cells. Consequently, TAS-116, one of the most evolved HSP90 inhibitor, may become a promising option against ATL therapy. Overall design: To identify differentially expressed genes after the treatment with TAS-116, ATL cell lines were treated with DMSO or TAS-116 for 16h. Then, total RNAs were collected from these cell lines and subsequently subjected to gene expression microarray analysis.xref:PubMed:34794206ENAAdult T-Cell, Adult T-Cell Leukemias, HTLV-1 associated adult T-cell lymphoma/leukemia, HTLV-I-Associated T-Cell Leukemia-Lymphoma, Activity, HTLV I Associated, postnatal development, Human T-Cell Leukemia-Lymphomas, adult T-cell lymphoma, adult T-cell leukemia/lymphoma (HTLV-1 positive), growth and development, T Cell Leukemia Lymphoma, T-Cell Leukemia-Lymphomas, Leukemias, T-Cell Leukemia, T-Cell Leukemias, Human, development, HTLV-I-Associated T-Cell Leukemia-Lymphomas, adult T cell lymphoma/leukemia, T-Cell, Adult T-Cell., Leukemia-Lymphoma, Human T Lymphotropic Virus-Associated Leukemia-Lymphoma, HTLV-Associated Leukemia-Lymphomas, Human T Cell Leukemia Lymphoma, T-Cell Leukemia-Lymphoma, Adult T-Cell Leukemia-Lymphoma, HTLV Associated Leukemia Lymphoma, Adult T-Cell Leukemia, HTLV-Associated, Leukemia Lymphoma, Leukemia, T Cell Leukemia, growth pattern, non-developmental growth, Human T-Cell Leukemia-Lymphoma, postnatal growth, HTLV-I-Associated T-Cell, Adult, adult T-cell lymphoma/leukemia, HTLV-Associated Leukemia-Lymphoma, Acute, HTLV I Associated T Cell Leukemia Lymphoma, Human T-Cell, HTLV-I associated adult T-cell leukemia/lymphoma, Human T Lymphotropic Virus Associated Leukemia Lymphoma, ATLL, HTLV-I-Associated, Adult T-Cell Leukemia-Lymphomas, T Cell, Leukemia-Lymphomas, growth, General activity, Adult T CellAdult T-Cell, Adult T-Cell Leukemias, HTLV-1 associated adult T-cell lymphoma/leukemia, HTLV-I-Associated T-Cell Leukemia-Lymphoma, Activity, HTLV I Associated, postnatal development, Human T-Cell Leukemia-Lymphomas, adult T-cell lymphoma, adult T-cell leukemia/lymphoma (HTLV-1 positive), growth and development, T Cell Leukemia Lymphoma, T-Cell Leukemia-Lymphomas, Leukemias, T-Cell Leukemia, T-Cell Leukemias, Human, development, HTLV-I-Associated T-Cell Leukemia-Lymphomas, adult T cell lymphoma/leukemia, T-Cell, Adult T-Cell., Leukemia-Lymphoma, Human T Lymphotropic Virus-Associated Leukemia-Lymphoma, HTLV-Associated Leukemia-Lymphomas, Human T Cell Leukemia Lymphoma, T-Cell Leukemia-Lymphoma, Adult T-Cell Leukemia-Lymphoma, HTLV Associated Leukemia Lymphoma, Adult T-Cell Leukemia, HTLV-Associated, Leukemia Lymphoma, Leukemia, T Cell Leukemia, growth pattern, non-developmental growth, Human T-Cell Leukemia-Lymphoma, postnatal growth, HTLV-I-Associated T-Cell, Adult, adult T-cell lymphoma/leukemia, HTLV-Associated Leukemia-Lymphoma, Acute, HTLV I Associated T Cell Leukemia Lymphoma, Human T-Cell, HTLV-I associated adult T-cell leukemia/lymphoma, Human T Lymphotropic Virus Associated Leukemia Lymphoma, ATLL, HTLV-I-Associated, Adult T-Cell Leukemia-Lymphomas, T Cell, Leukemia-Lymphomas, growth, General activity, Adult T CellfalseHighly selective HSP90 inhibitor, pimitespib, demonstrates its potent growth suppressive activity to adult T-cell leukemia in preclinical models (Su9T01).Highly selective HSP90 inhibitor, pimitespib, demonstrates its potent growth suppressive activity to adult T-cell leukemia in preclinical models (Su9T01).2025-09-242022-02-21PRJNA708289GSE168558960634794206