RRC ID 60998
Author Noura M, Matsuo H, Koyama A, Adachi S, Masutani H.
Title TXNIP induces growth arrest and enhances ABT263-induced apoptosis in mixed-lineage leukemia-rearranged acute myeloid leukemia cells.
Journal FEBS Open Bio
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.
Volume 10(8)
Pages 1532-1541
Published 2020-8-1
DOI 10.1002/2211-5463.12908
PMID 32511893
PMC PMC7396447
MeSH Aniline Compounds / pharmacology Antineoplastic Agents / pharmacology Apoptosis / drug effects Carrier Proteins / genetics Carrier Proteins / metabolism* Cell Cycle Checkpoints / drug effects Cell Line, Tumor Cell Proliferation / drug effects Humans Leukemia, Myeloid, Acute / drug therapy Leukemia, Myeloid, Acute / metabolism* Leukemia, Myeloid, Acute / pathology Sulfonamides / pharmacology
IF 2.231
Times Cited 0
DNA material CSIV-TRE-RfA-UbC-KT (RDB12878)