Article
Plant Sciences
Xiaoying Lan, Min Hu, Liling Jiang, Jiamin Wang, Yi Meng, Xinmei Chen, Aochu Liu, Wa Ding, Haichuan Zhang, Huan Zhou, Bingyuan Liu, Guanjie Peng, Siyan Liao, Xin Chen, Jinbao Liu, Xianping Shi
Summary: The natural substance piperlongumine from the herbal medicine Piper longum L. has been found to overcome imatinib resistance in chronic myelogenous leukemia (CML), providing a new therapeutic strategy.
JOURNAL OF ETHNOPHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Tingting Lu, Jiangyan Cao, Fengming Zou, Xixiang Li, Aoli Wang, Wenliang Wang, Huamin Liang, Qingwang Liu, Chen Hu, Cheng Chen, Zhenquan Hu, Wenchao Wang, Lili Li, Jian Ge, Yang Shen, Tao Ren, Jing Liu, Ruixiang Xia, Qingsong Liu
Summary: CHMFL-48 is a novel type II kinase inhibitor that potently inhibits the wild-type BCR-ABL kinase and a panel of imatinib-resistant mutants. This drug shows strong inhibitory activity in a cellular context, blocking autophosphorylation of BCR-ABL kinase, affecting downstream signaling mediators, and inducing cell cycle progression blockade and apoptosis.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Lihong Ding, Qinwei Chen, Kai Chen, Yuelong Jiang, Genhong Li, Qiuling Chen, Dongyu Bai, Dehong Gao, Manman Deng, Haiping Zhang, Bing Xu
Summary: Constitutively activated BCR-ABL kinase is the driver event in chronic myeloid leukemia (CML) development. Imatinib, the first BCR-ABL inhibitor, has improved clinical outcomes, but resistance occurs in 25-30% of patients. Simvastatin, a HMG-CoA reductase inhibitor, shows antitumor effects and acts as a sensitizer to kill imatinib-resistant and T315I mutated CML cells.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Hematology
Huimin Feng, Yue Fu, Zelong Cui, Minran Zhou, Lu Zhang, Zhenxing Gao, Sai Ma, Chunyan Chen
Summary: This study shows that PHF8 is significantly increased in CML patients and inhibits cell differentiation while promoting cell proliferation. Targeting PHF8, which directly regulates BCR::ABL1 expression, may be a useful therapeutic approach for CML.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Oncology
Yun Xu, Ziting Wang, Lei Zhang, Congying Gao, Fahui Li, Xueming Li, Yu Ke, Hong-Min Liu, Zhenbo Hu, Liuya Wei, Zhe-Sheng Chen
Summary: The compound JOA can inhibit the proliferation of chronic myeloid leukemia cells, including those with the BCR-ABL-T315I mutation, and induce cell differentiation. This effect may be mediated by the inhibition of the BCR-ABL/c-MYC signaling pathway. JOA shows potential as a lead compound for overcoming imatinib resistance in CML therapy.
Article
Hematology
Buket Altinok Gunes, Yalda Hekmatshoar, Tulin Ozkan, Sureyya Bozkurt, O. Sena Erdogan Aydos, Yahya Buyukasik, Elifcan Aladag, Asuman Sunguroglu
Summary: This study investigated the possible genetic resistance mechanisms in patients developing resistance to Imatinib mesylate (IMA) therapy, and found that SCD-1 and BCL-2 genes may be involved in resistance.
MEDITERRANEAN JOURNAL OF HEMATOLOGY AND INFECTIOUS DISEASES
(2023)
Article
Oncology
Zhen Liu, Wenlong Zheng, Yuan Liu, Binghe Zhou, Yuqing Zhang, Fan Wang
Summary: The study showed that HSPA8 is overexpressed in imatinib-resistant CML cells and its ablation can inhibit cell proliferation, induce autophagy, and enhance the anti-tumor activity of imatinib. These findings reveal the role of HSPA8 in IR-CML and suggest its potential as a target for treatment.
EXPERIMENTAL CELL RESEARCH
(2021)
Article
Multidisciplinary Sciences
Yosuke Tanaka, Reina Takeda, Tsuyoshi Fukushima, Keiko Mikami, Shun Tsuchiya, Moe Tamura, Keito Adachi, Terumasa Umemoto, Shuhei Asada, Naoki Watanabe, Soji Morishita, Misa Imai, Masayoshi Nagata, Marito Araki, Hitoshi Takizawa, Tomofusa Fukuyama, Chrystelle Lamagna, Esteban S. Masuda, Ryoji Ito, Susumu Goyama, Norio Komatsu, Tomoiku Takaku, Toshio Kitamura
Summary: Leukemia stem cells in chronic myeloid leukemia are resistant to imatinib, but can be eliminated by combining imatinib with IRAK1/4 inhibitors that inhibit the IRAK1/4-NF-kappa B-PD-L1 signaling pathway.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Rachid Lahlil, Anne Aries, Maurice Scrofani, Celine Zanetti, Desline Hennequin, Bernard Drenou
Summary: Chronic myeloid leukemia (CML) is a clonal myeloproliferative disease characterized by the presence of the BCR-ABL fusion gene. Treatment with tyrosine kinase inhibitors (TKIs) such as imatinib mesylate (IM) has significantly improved clinical outcomes for CML patients, but IM resistance remains a major challenge. The cause of IM resistance in CML cells is unclear, but additional genetic alterations in leukemic stem cells (LSCs) are a common cause of relapse. A study found that a rare subpopulation of stem cells called very small embryonic-like stem cells (VSELs) in adult CML patients is resistant to IM and less sensitive to apoptosis compared to leukemic hematopoietic stem cells (HSCs). The expression levels of certain miRNAs are also affected in these IM-resistant VSELs, including miR-126 and miR-21, which are involved in LSC leukemia-initiating capacity and growth.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Jin-Man Zhang, Cui-Fang Wang, Mei-Yan Wei, Hui Dong, Yu-Cheng Gu, Xiao-Mei Mo, Chang-Lun Shao, Ming Liu
Summary: In this study, we found that Brefeldin A (BFA) is a cytotoxic compound that inhibits the activation of BCR-ABL and degrades the BCR-ABL protein in K562 cells, thereby suppressing the development of CML.
ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY
(2022)
Article
Medicine, General & Internal
Lu Gao, Ming-qiang Ren, Zu-guo Tian, Zhi-yuan Peng, Genghui Shi, Zhong Yuan
Summary: Chronic myelogenous leukemia patients with thrombocytosis and complex chromosomal translocation are extremely rare, and treatment with imatinib may be the preferred option. Performing BCR/ABL fusion gene examination can be an effective strategy to avoid misdiagnosis in patients with thrombocytosis.
Article
Pharmacology & Pharmacy
Congying Gao, Lei Zhang, Yun Xu, Xiangyu Ma, Peilei Chen, Zhe-Sheng Chen, Liuya Wei
Summary: In this study, the potent histone deacetylase inhibitor I13 was assessed for its effect on chronic myeloid leukemia (CML) cells harboring T315I-mutated and wild-type BCR-ABL. I13 showed strong activity against both types of cells, inducing cell differentiation and suppressing proliferation by causing cell cycle G0/G1-phase accumulation. It was found that I13 blocked the CML signaling pathway by depleting BCR-ABL, resulting in cell differentiation. These findings highlight I13 as a BCR-ABL modulator for overcoming drug resistance caused by T315I-mutated BCR-ABL and have implications for CML therapy development.
FRONTIERS IN PHARMACOLOGY
(2023)
Review
Oncology
Anna Sicuranza, Donatella Raspadori, Monica Bocchia
Summary: CD26/DPP-4 is a membrane-bound multifunctional protein that is expressed in many solid tumors and hematological malignancies, and recent investigations have shown its specific expression on leukemic stem cells of Chronic Myeloid Leukemia. This finding suggests that CD26 could be a potential marker for monitoring therapeutic responses in CML patients receiving Tyrosine Kinase Inhibitors treatment. Preliminary data from a multicenter study in Italy indicated that CML patients with a poorer response had a higher number of CD26+ LSCs at diagnosis, confirming the specificity of CD26 as a marker in CML.
Review
Hematology
Naranie Shanmuganathan, Timothy P. Hughes
Summary: The recent approval of asciminib as a treatment option for CML patients provides clinicians with more choices for therapy. Asciminib is a highly potent BCR-ABL1 inhibitor with limited off-target effects, but its position among other available TKIs is still unclear. There are many unanswered questions about the optimal use of asciminib.
BRITISH JOURNAL OF HAEMATOLOGY
(2022)
Article
Oncology
Angela McLigeyo, Jamilla Rajab, Peter Oyiro, Mohammed Ezzi, Yatich Bett, Matilda Ong'ondi, Andrew Odhiambo, Sitna Mwanzi, Nicholas Othieno-Abinya
Summary: This study analyzed the baseline characteristics and factors associated with cytopenia in Chronic Myeloid Leukemia patients treated with imatinib. The results showed no significant differences in gender, age, marital status, occupation, and education level between patients with and without cytopenia. Multivariable analysis revealed that baseline anemia, neutropenia, thrombocytopenia, and thrombocytosis increased the odds of developing cytopenia.
Article
Cell Biology
Xinxin Song, Jiao Liu, Feimei Kuang, Xin Chen, Herbert J. Zeh, Rui Kang, Guido Kroemer, Yangchun Xie, Daolin Tang
Summary: Glucose determines the sensitivity of human pancreatic ductal carcinoma cells to ferroptosis and PDK4 is identified as the top gene responsible for ferroptosis resistance. Inhibiting PDK4 enhances the anticancer activity of system xc(-) inhibitors in vitro and in suitable preclinical mouse models. These findings suggest metabolic reprogramming as a potential target for overcoming ferroptosis resistance.
Article
Chemistry, Multidisciplinary
Da-cai Xu, Li Yang, Pei-quan Zhang, Ding Yan, Qian Xue, Qing-tian Huang, Xiao-fen Li, Ya-li Hao, Dao-lin Tang, Q. Ping Dou, Xin Chen, Jin-bao Liu
Summary: The study synthesized a novel gold (I) complex named Na-AuPT that exhibited high water solubility and potent inhibitory effects on the growth of multiple cancer cell lines, as well as induction of apoptosis. In nude mice bearing xenografts, Na-AuPT administration significantly inhibited tumor growth and induced cell death of primary mononuclear cells from patients with acute myeloid leukemia, suggesting its potential as a promising metal-based proteasome inhibitor for cancer therapy.
ACTA PHARMACOLOGICA SINICA
(2022)
Article
Cell Biology
Xin Chen, Xinxin Song, Jingbo Li, Ruoxi Zhang, Chunhua Yu, Zhuan Zhou, Jiao Liu, Siyan Liao, Daniel J. Klionsky, Guido Kroemer, Jinbao Liu, Daolin Tang, Rui Kang
Summary: This study identifies HPCAL1 as a novel autophagy receptor for the selective degradation of CDH2 during ferroptosis. Depletion of CDH2 increases susceptibility to ferroptotic death. The phosphorylation of HPCAL1 and the non-classical LC3-interacting region motif play key roles in the autophagic degradation of CDH2. A ferroptosis inhibitor is found to suppress HPCAL1 expression. Inhibition of HPCAL1 prevents ferroptosis-induced tumor suppression and pancreatitis in mouse models.
Article
Biochemistry & Molecular Biology
Bingchuan Geng, Xiaoliang Wang, Ki Ho Park, Kyung Eun Lee, Jongsoo Kim, Peng Chen, Xinyu Zhou, Tao Tan, Chunlin Yang, Xunchang Zou, Paul M. Janssen, Lei Cao, Lei Ye, Xuejun Wang, Chuanxi Cai, Hua Zhu
Summary: In this study, it was found that UCHL1 plays a protective role in myocardial infarction (MI) by stabilizing HIF-1α and promoting HIF-1α signaling. The absence of UCHL1 makes cardiomyocytes more susceptible to hypoxia/re-oxygenation induced injury.
Editorial Material
Biochemistry & Molecular Biology
Xin Chen, Chiara Nardon, Q. Ping Dou
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Cardiac & Cardiovascular Systems
Penglong Wu, Yifan Li, Mingqi Cai, Bo Ye, Bingchuan Geng, Faqian Li, Hua Zhu, Jinbao Liu, Xuejun Wang
Summary: This study found that UCHL1 plays a crucial protective role in cardiomyocytes by promoting autophagy and reducing cardiac dysfunction after myocardial infarction.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Article
Oncology
Leyi Yao, Qian Zhao, Ding Yan, Ziying Lei, Yali Hao, Jinghong Chen, Qian Xue, Xiaofen Li, Qingtian Huang, Daolin Tang, Q. Ping Dou, Xin Chen, Jinbao Liu
Summary: This study reveals the antagonistic effect of bilirubin on the anticancer activity of sorafenib in HCC. Bilirubin can predict the efficacy of sorafenib treatment by interfering with its inhibitory effects on cell proliferation and induction of apoptosis.
CANCER BIOLOGY & MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Lei Zhang, Taixing Cui, Xuejun Wang
Summary: Recent studies have revealed a complex interplay between autophagy and regulated necrosis, providing new insights into the pathophysiology of related diseases. Understanding the intricate relationship between these processes at the molecular level is crucial for further research and potential therapeutic implications in various pathological conditions.
ANTIOXIDANTS & REDOX SIGNALING
(2023)
Article
Multidisciplinary Sciences
Xin Chen, Jun Huang, Chunhua Yu, Jiao Liu, Wanli Gao, Jingbo Li, Xinxin Song, Zhuan Zhou, Changfeng Li, Yangchun Xie, Guido Kroemer, Jinbao Liu, Daolin Tang, Rui Kang
Summary: The authors discovered that the translation initiation factor eIF4E can increase lipid peroxidation levels and promote ferroptosis by repressing ALDH1B1 independent of translation. This finding provides insights into the mechanisms of ferroptosis and establishes a foundation for utilizing ferroptosis as a cancer therapeutic strategy.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Qian Xue, Ding Yan, Xi Chen, Xiaofen Li, Rui Kang, Daniel J. J. Klionsky, Guido Kroemer, Xin Chen, Daolin Tang, Jinbao Liu
Summary: Ferroptosis is an iron-dependent regulated cell death characterized by lipid peroxidation and membrane damage. Copper promotes ferroptotic cell death by inducing autophagic degradation of GPX4. These findings provide new insights into the connection between metal stress and autophagy-dependent cell death.
Article
Plant Sciences
Xiaoying Lan, Min Hu, Liling Jiang, Jiamin Wang, Yi Meng, Xinmei Chen, Aochu Liu, Wa Ding, Haichuan Zhang, Huan Zhou, Bingyuan Liu, Guanjie Peng, Siyan Liao, Xin Chen, Jinbao Liu, Xianping Shi
Summary: The natural substance piperlongumine from the herbal medicine Piper longum L. has been found to overcome imatinib resistance in chronic myelogenous leukemia (CML), providing a new therapeutic strategy.
JOURNAL OF ETHNOPHARMACOLOGY
(2023)
Review
Cell Biology
Qian Xue, Rui Kang, Daniel J. Klionsky, Daolin Tang, Jinbao Liu, Xin Chen
Summary: Copper is an essential trace element that regulates enzymes and transcription factors, but high concentrations can lead to cell death and autophagy. Abnormal copper metabolism is associated with various diseases, including Wilson disease and cancer, and copper-based compounds have potential therapeutic applications. Understanding copper metabolic processes may enhance cancer diagnosis and treatment.
Article
Cardiac & Cardiovascular Systems
Liuqing Yang, Nirmal Parajuli, Penglong Wu, Jinbao Liu, Xuejun Wang
Summary: The study establishes that PKA activates 26S proteasomes through pS14-Rpn6 and identifies pS14-Rpn6 as a key factor in cardiac proteinopathy.
CIRCULATION RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Leyi Yao, Ding Yan, Baoyi Jiang, Qian Xue, Xi Chen, Qingtian Huang, Ling Qi, Daolin Tang, Xin Chen, Jinbao Liu
Summary: Plumbagin, a natural product, inhibits the growth of hepatocellular carcinoma cells by downregulating GPX4 and inducing its ubiquitination and degradation. This novel mechanism highlights the potential therapeutic value of plumbagin in treating liver cancer.
FREE RADICAL BIOLOGY AND MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Qianqian Yang, Ding Yan, Chaoying Zou, Qian Xue, Shuhui Lin, Qingtian Huang, Xiaofen Li, Daolin Tang, Xin Chen, Jinbao Liu
Summary: A novel therapeutic target, STAMBP, has been identified for the treatment of triple-negative breast cancer (TNBC). This study reveals that STAMBP promotes TNBC growth and progression by stabilizing the RAI14 protein. Moreover, high levels of STAMBP are associated with poor prognosis in TNBC patients.
EXPERIMENTAL AND MOLECULAR MEDICINE
(2022)