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Title: TXNIP induces growth arrest and enhances ABT263‐induced apoptosis in mixed‐lineage leukemia‐rearranged acute myeloid leukemia cells
Authors: Noura, Mina
Matsuo, Hidemasa  kyouindb  KAKEN_id  orcid (unconfirmed)
Koyama, Asami
Adachi, Souichi
Masutani, Hiroshi
Author's alias: 能浦, 三奈
松尾, 英将
小山, 朝美
足立, 壯一
増谷, 弘
Keywords: AML
Issue Date: Aug-2020
Publisher: Wiley
Journal title: FEBS Open Bio
Volume: 10
Issue: 8
Start page: 1532
End page: 1541
Abstract: Thioredoxin‐interacting protein (TXNIP) has been widely recognized as a tumor suppressor in various cancers, including liver, breast, and thyroid cancers. Although TXNIP is epigenetically silenced in acute myeloid leukemia (AML) cells, as in many cancer cells, its role in leukemogenesis remains elusive. Mixed‐lineage leukemia (MLL) gene rearrangements in AML are associated with poor prognosis, and the development of a new treatment method is eagerly anticipated. In this study, we first reveal that lower expression of TXNIP is correlated with shortened overall survival periods in AML patients. Moreover, we demonstrated that TXNIP overexpression significantly suppresses proliferation in AML cells harboring MLL fusion genes. TXNIP promotes autophagy by increasing expression of the autophagy protein, Beclin 1, and lipidation of LC3B. We also show that TXNIP overexpression combined with ABT263, a potent inhibitor of Bcl‐2 and Bcl‐xL, is highly effective at inducing cell death in MLL‐rearranged (MLL‐r) AML cells. In summary, this study provides insights into the molecular mechanism of TXNIP‐mediated tumor suppression and furthermore underscores the potential of TXNIP as a promising therapeutic target for MLL‐r AML.
Rights: © 2020 The Authors. Published by FEBS Press and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
DOI(Published Version): 10.1002/2211-5463.12908
PubMed ID: 32511893
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