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
Immunology
Anila Vadakumchery, Hemin Faraidun, Omar El Ayoubi, Issame Outaleb, Vera Schmid, Hend Abdelrasoul, Timm Amendt, Ahmad Khadour, Corinna Setz, Katharina Goehring, Karoline Lodd, Christoffer Hitzing, Alabbas Alkhatib, Mayas Bilal, Julian Benckendorff, Abdul Kader Al Shugri, Cord Herbert Brakebusch, Niklas Engels, Moumita Datta, Elias Hobeika, Ameera Alsadeq, Hassan Jumaa
Summary: The adaptor protein SLP65 controls the down-regulation of PI3K signaling in B cells by inducing the activity of small GTPase RHOA, which activates the negative regulator PTEN. RHOA plays a unique role in B cell generation and selection, and blocking its function offers potential for treating B cell malignancies.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Bohan Ma, Hui Feng, Chao Feng, Yi Liu, Hailing Zhang, Jincheng Wang, Wenjuan Wang, Pengcheng He, Fan Niu
Summary: The study designed a dual-targeting proteolysis-targeting chimera (PROTAC) type drug that can induce Bcr/Abl degradation and activate the p53 pathway simultaneously, potentially overcoming drug resistance in Ph+ leukemias.
Article
Plant Sciences
Hoang Thanh Chi, Nguyen Thi Lien Thuong, Bui Thi Kim Ly
Summary: The study found that the methanol extract of Sphagneticola trilobata (L.) Pruski (MeST) has an inhibitory effect on the growth of leukemia cells, especially those harboring imatinib-resistant BCR/ABL. The cell death induced by MeST is through apoptosis and it can also suppress the expression of the BCR/ABL protein.
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
Oncology
Karoline Gleixner, Yuksel Filik, Daniela Berger, Christina Schewzik, Gabriele Stefanzl, Irina Sadovnik, Lina Degenfeld-Schonburg, Gregor Eisenwort, Mathias Schneeweiss-Gleixner, Konstantin Byrgazov, Wolfgang R. Sperr, Jiri Mayer, Thomas Lion, Peter Valent
Summary: Research shows that the combination of asciminib and ponatinib has a synergistic effect on inducing apoptosis in CML cells, especially effective against cells with T315I+ BCR-ABL1 compound mutations, with further enhanced anti-leukemic effects when used in combination with HU.
AMERICAN JOURNAL OF CANCER RESEARCH
(2021)
Article
Pharmacology & Pharmacy
Hong Zhang, Ting Song, Ziqian Wang, Yafei Guo, Hang Wang, Qishuang Gao, Zhichao Zhang, Uwituze Laura Bonneete
Summary: By using a specific inhibitor of Hsp70/Bim complex and knocking down Bcr-Abl, researchers have found that Bcr-Abl can prevent cell apoptosis by driving the formation of Hsp70/Bim complex. Additionally, Bcr-Abl can stabilize oncogenic clients by driving the formation of Hsp70/Bim complex.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Yuan Tan, Zhenglan Huang, Xin Wang, Hongdan Dai, Guoyun Jiang, Wenli Feng
Summary: This study identified a novel fusion circRNA (F-circBA1) originating from BCR-ABL, which is mainly localized in the cytoplasm and plays an oncogenic role in CML cells.
Article
Biochemistry & Molecular Biology
Elena Vuelta, Jose L. Ordonez, David J. Sanz, Sandra Ballesteros, Jesus M. Hernandez-Rivas, Lucia Mendez-Sanchez, Manuel Sanchez-Martin, Ignacio Garcia-Tunon
Summary: This study demonstrates the therapeutic potential of a CRISPR-Trap system as a novel strategy for gene elimination in haematological neoplasms. The CRISPR-Trap efficiently interrupts the coding sequence of the oncogene and allows for the selection of edited cells. In vitro and in vivo experiments show the therapeutic benefit of this system.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Daisuke Koyama, Jiro Kikuchi, Yoshiaki Kuroda, Masatsugu Ohta, Yusuke Furukawa
Summary: This study reveals the critical role of metabolic homeostasis in the survival of CML cells, particularly in advanced stages of the disease. The BCR-ABL protein activates AMP-activated protein kinase and the mTOR pathway to regulate ATP production and autophagy, with nuclear BCR-ABL detected in advanced-stage CML cells. Activation of AMPK triggers autophagy under energy-deprived conditions, leading to cytoplasmic translocation of BCR-ABL and eventual apoptotic cell death when intracellular ATP is exhausted. This pathway represents a novel therapeutic vulnerability for treating TKI-resistant CML.
Article
Chemistry, Medicinal
Haixia Liu, Xinyu Ding, Linyi Liu, Qianglong Mi, Quanju Zhao, Yubao Shao, Chaowei Ren, Jinju Chen, Ying Kong, Xing Qiu, Nicola Elvassore, Xiaobao Yang, Qianqian Yin, Biao Jiang
Summary: Protein degradation through CRBN-recruiting PROTACs has shown promising potential in targeting oncogenic fusion protein BCR-ABL, providing a potential therapeutic strategy for chronic myeloid leukemia.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Cell Biology
Yuhang Peng, Zhenglan Huang, Fangzhu Zhou, Teng Wang, Ke Mou, Wenli Feng
Summary: The study identified that HSP90AB1 interacts with the CC domain of Bcr-Abl via its N-terminal domain, preventing the transport of Bcr-Abl protein to the nucleus, and subsequently inhibiting the proliferation and inducing apoptosis of CML cells. Targeting the NTD of HSP90AB1 to inhibit its interaction with Bcr-Abl could be a more precise approach for the development and application of HSP90 inhibitors in CML treatment.
CELL COMMUNICATION AND SIGNALING
(2021)
Article
Immunology
Si-Yu Yang, Jie Long, Meng-Xing Huang, Pan-Yue Luo, Zhen-Hua Bian, Ya-Fei Xu, Cheng-Bo Wang, Shu-Han Yang, Liang Li, Carlo Selmi, M. Eric Gershwin, Zhi-Bin Zhao, Zhe-Xiong Lian
Summary: Regulatory B cells (Breg) are immunosuppressive cells with different subsets identified in various organs. This study used high-throughput single-cell RNA sequencing and B-cell receptor sequencing to define the phenotype of Breg cells. The research revealed organ-specific subsets of Breg cells, with non-B10 Breg cells exhibiting unique immunosuppressive properties linked to TGF-beta pathway activation.
FRONTIERS IN IMMUNOLOGY
(2021)
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
Oncology
Liling Jiang, Qingyan He, Xin Chen, Aochu Liu, Wa Ding, Haichuan Zhang, Xinmei Chen, Huan Zhou, Yi Meng, Bingyuan Liu, Guanjie Peng, Chunyan Wang, Jinbao Liu, Xianping Shi
Summary: This study found that the proteasomal deubiquitinases USP14 and UCHL5 were overexpressed in primary cancer cells from CML patients. The inhibitor of USP14 and UCHL5, b-AP15, displayed potent tumor-killing activity in BCR-ABL(WT) and BCR-ABL(T315I) CML cell lines, as well as in CML xenografts and primary CML cells. Inhibition of USP14 and UCHL5, either pharmacologically or genetically, induced cell apoptosis and decreased the protein level of BCR-ABL in CML cells expressing BCR-ABL(WT) and BCR-ABL(T315I). Moreover, b-AP15 synergistically enhanced the cytotoxic effect of TKI imatinib in BCR-ABL(WT) and BCR-ABL(T315I) CML cells.
CLINICAL AND TRANSLATIONAL MEDICINE
(2022)