一二三四区视频,亚洲少妇熟女色,日本久热无码视频网,欧美国产日韩大尺度,亚洲a视频,久久少妇一区二区,日韩999无码视频,刺激久久久久久久,啊啊啊啊不要啊在线

ChemicalBook >> journal list >> Cell Death & Disease >>article
Cell Death & Disease

Cell Death & Disease

IF: 8.1
Download PDF

BCR-ABL triggers a glucose-dependent survival program during leukemogenesis through the suppression of TXNIP

Published:24 April 2023 DOI: 10.1038/s41419-023-05811-2 PMID: 37095099
Lin Feng, Ruxin Ding, Xuan Qu, Yuanchun Li, Tong Shen, Lei Wang, Ruikai Li, Juan Zhang, Yi Ru, Xin Bu, Yang Wang, Min Li, Wenqi Song, Liangliang Shen, Pengxia Zhang

Abstract

Imatinib is highly effective in the treatment of chronic myelogenous leukemia (CML), but the primary and acquired imatinib resistance remains the big hurdle. Molecular mechanisms for CML resistance to tyrosine kinase inhibitors, beyond point mutations in BCR-ABL kinase domain, still need to be addressed. Here, we demonstrated that thioredoxin-interacting protein (TXNIP) is a novel BCR-ABL target gene. Suppression of TXNIP was responsible for BCR-ABL triggered glucose metabolic reprogramming and mitochondrial homeostasis. Mechanistically, Miz-1/P300 complex transactivates TXNIP through the recognition of TXNIP core promoter region, responding to the c-Myc suppression by either imatinib or BCR-ABL knockdown. TXNIP restoration sensitizes CML cells to imatinib treatment and compromises imatinib resistant CML cell survival, predominantly through the blockage of both glycolysis and glucose oxidation which results in the mitochondrial dysfunction and ATP production. In particular, TXNIP suppresses expressions of the key glycolytic enzyme, hexokinase 2 (HK2), and lactate dehydrogenase A (LDHA), potentially through Fbw7-dependent c-Myc degradation. In accordance, BCR-ABL suppression of TXNIP provided a novel survival pathway for the transformation of mouse bone marrow cells. Knockout of TXNIP accelerated BCR-ABL transformation, whereas TXNIP overexpression suppressed this transformation. Combination of drug inducing TXNIP expression with imatinib synergistically kills CML cells from patients and further extends the survival of CML mice. Thus, the activation of TXNIP represents an effective strategy for CML treatment to overcome resistance.

Similar articles

IF:4.8

Rocaglamide reprograms glucose metabolism in erythroleukemic cells via c-MYC transcriptional regulation of TXNIP and HK2

Journal of ethnopharmacology Jialei Song, Wuling Liu,etc Published: 21 November 2024
IF:4.7

TRPV4 couples with NCX1 to mediate glucose‐dependent glucagon‐like peptide‐1 release and improve glucose homeostasis

Journal of Physiology-London Xiongying Chen, Fenglan Chu,etc Published: 21 November 2024
IF:6

PhNH10 Suppresses Low Temperature Tolerance in Petunia Through the Abscisic Acid‐Dependent Pathway

Plant, Cell & Environment Hongzhuang Niu, Xueqi Liu,etc Published: 20 November 2024
荥阳市| 类乌齐县| 苍山县| 商丘市| 霍城县| 镇坪县| 胶州市| 湖南省| 通山县| 磐安县| 日喀则市| 黄石市| 瑞安市| 揭东县| 通江县| 营山县| 台州市| 中卫市| 登封市| 双流县| 保山市| 广昌县| 邵阳市| 宁蒗| 宁安市| 淅川县| 儋州市| 福泉市| 鄂托克前旗| 屯留县| 体育| 铁力市| 乡宁县| 吉安县| 吴川市| 天等县| 万载县| 司法| 精河县| 宁强县| 公主岭市|