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
Cell Biology
Chang Liu, Waiyi Zou, Danian Nie, Shuyi Li, Chen Duan, Min Zhou, Peilong Lai, Shengyong Yang, Sen Ji, Yangqiu Li, Mei Mei, Shilai Bao, Yanli Jin, Jingxuan Pan
Summary: This study investigates the role of PRMT family member PRMT7 in the maintenance of leukemia stem cells (LSCs) in chronic myeloid leukemia (CML). The research shows that targeting PRMT7 delays leukemia development and impairs self-renewal of LSCs without affecting normal hematopoiesis. Mechanistically, loss of PRMT7 leads to reprogramming of glycine metabolism, generating methylglyoxal which is detrimental to LSCs. These findings suggest PRMT7 as a potential therapeutic target for eradicating LSCs in CML.
Article
Medicine, Research & Experimental
Mansi Shah, Harish Kumar, Shaowei Qiu, Hui Li, Mason Harris, Jianbo He, Ajay Abraham, David K. Crossman, Andrew Paterson, Robert S. Welner, Ravi Bhatia
Summary: In chronic myeloid leukemia (CML), LT-HSCs expressing low c-KIT levels are primitive, quiescent, and drug-resistant leukemia-initiating cells, representing a critical target for eliminating disease persistence.
Article
Biochemistry & Molecular Biology
Elena V. Koroleva, Yuri V. Kornoushenko, Anna D. Karpenko, Ivan P. Bosko, Julia V. Siniutsich, Zhanna V. Ignatovich, Alexander M. Andrianov
Summary: An integrated computational approach was used to identify potential inhibitors of Bcr-Abl tyrosine kinase, an enzyme involved in chronic myeloid leukemia. Five compounds were found to effectively block the enzyme activity and exhibit high binding affinity comparable to FDA-approved kinase inhibitors. These compounds may serve as good scaffolds for the design of novel anticancer agents.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2023)
Review
Cell & Tissue Engineering
Hanieh Mojtahedi, Niloufar Yazdanpanah, Nima Rezaei
Summary: CML is driven by the BCR-ABL1 oncoprotein, and TKI therapy has been successful. However, mechanisms leading to resistance and disease progression in CML LSCs call for targeted therapies to eradicate them.
STEM CELL RESEARCH & THERAPY
(2021)
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
Chemistry, Medicinal
You-lu Pan, Shen-xin Zeng, Rong-rong Hao, Mei-hao Liang, Zheng-rong Shen, Wen-hai Huang
Summary: This review summarizes the current research progress of inhibitors and degraders targeting BCR-ABL for the treatment of CML, including first, second, and third-generation tyrosine kinase inhibitors targeting different mutations, as well as allosteric inhibitors and proteolysis-targeting chimeras (PROTAC) based on different E3 ligands.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Oncology
Stephanie Sembill, Maria Ampatzidou, Sonali Chaudhury, Michael Dworzak, Krzysztof Kalwak, Axel Karow, Alexander Kiani, Manuela Krumbholz, Maaike Luesink, Nora Naumann-Bartsch, Barbara De Moerloose, Michael Osborn, Kirk R. Schultz, Petr Sedlacek, Fiorina Giona, Christian Michel Zwaan, Hiroyuki Shimada, Birgitta Versluijs, Frederic Millot, Nobuko Hijiya, Meinolf Suttorp, Markus Metzler
Summary: The treatment of chronic myeloid leukemia has improved with the use of tyrosine kinase inhibitors; however, the prognosis for CML in the blast phase remains poor and treatment options are limited. In order to provide consistent therapy for children and adolescents with this high-risk disease, an international panel of pediatric CML experts developed recommendations based on current literature and national standards.
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
Oncology
Ryan Yen, Sarah Grasedieck, Andrew Wu, Hanyang Lin, Jiechuang Su, Katharina Rothe, Helen Nakamoto, Donna L. Forrest, Connie J. Eaves, Xiaoyan Jiang
Summary: This study analyzed differentially expressed miRNAs in CML patients, showing that the combination of miR-145 and miR-708 effectively predicts response to NL in treatment-naive patients, while miR-150 and miR-185 are significant classifiers at 1 month and 3 months post-NL therapy.
Article
Oncology
Melanie Langhammer, Julia Schoepf, Timo Jaquet, Katharina Horn, Moritz Angel, Corinna Spohr, Daniel Christen, Franziska Maria Uhl, Tiago Maie, Henrike Jacobi, Thorsten B. Feyerabend, Julia Huber, Marcus Panning, Cassian Sitaru, Ivan Costa, Robert Zeiser, Konrad Aumann, Heiko Becker, Till Braunschweig, Steffen Koschmieder, Khalid Shoumariyeh, Michael Huber, Mirle Schemionek-Reinders, Tilman Brummer, Sebastian Halbach
Summary: The persistence of leukemic stem cells (LSCs) in chronic myeloid leukemia (CML) presents a challenge in therapy. This study investigates the role of mast cells (MCs) in CML progression and suggests targeting MCs as an additional approach for CML treatment. The BCR::ABL1 fusion gene drives the expansion of bone marrow-derived MCs and enhances their responsiveness to degranulation triggers. In CML patients, splenomegaly is associated with increased BM MC counts and elevated pro-inflammatory cytokines, indicating the importance of MCs in disease progression.
Article
Multidisciplinary Sciences
R. C. Nayak, K. H. Chang, A. K. Singh, M. Kotliar, M. Desai, A. M. Wellendorf, M. Wunderlich, J. Bartram, B. Mizukawa, M. Cuadrado, P. Dexheimer, A. Barski, X. R. Bustelo, N. N. Nassar, J. A. Cancelas
Summary: This study investigates the function of leukemic VAV3 in Ph+ and Ph-like B-ALL and reveals that nuclear VAV3 controls repressive transcriptional activity through the AKT/PHLPP2-BMI1 pathway. The findings highlight the importance of non-canonical nuclear Rho GTPase signaling in leukemogenesis.
NATURE COMMUNICATIONS
(2022)
Article
Engineering, Biomedical
Qiang Qiu, Linyu Yang, Yunyu Feng, Zejiang Zhu, Ning Li, Li Zheng, Yuanyuan Sun, Cong Pan, Huandi Qiu, Xue Cui, Wei He, Fang Wang, Yuyao Yi, Minghai Tang, Zhuang Yang, Yunfan Yang, Zhihui Li, Lijuan Chen, Yiguo Hu
Summary: Purinostat Mesylate (PM) is a highly selective and active HDAC I/IIb inhibitor. The injectable formulation of PM (PMF) with cyclodextrin can overcome PM's poor solubility and improve its stability and pharmacokinetic properties. PM effectively represses the survival of leukemia cells and PMF significantly prevents CML progression by targeting leukemia stem cells (LSCs).
BIOACTIVE MATERIALS
(2023)
Editorial Material
Hematology
Charles A. Schiffer
Summary: The outlook for patients with chronic phase chronic myelogenous leukemia (CML) has significantly improved in recent years with the development of oral tyrosine kinase inhibitors (TKIs). A study comparing asciminib and bosutinib in chronic phase CML patients previously treated with >= 2 TKIs may offer a better management option for this patient population.
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
Pharmacology & Pharmacy
Paola Orlandi, Marta Banchi, Francesca Vaglini, Marco Carli, Stefano Aringhieri, Arianna Bandini, Carla Pardini, Cristina Viaggi, Michele Lai, Greta Ali, Alessandra Ottani, Eleonora Vandini, Patrizia Guidi, Margherita Bernardeschi, Veronica La Rocca, Giulio Francia, Gabriella Fontanini, Mauro Pistello, Giada Frenzilli, Daniela Giuliani, Marco Scarselli, Guido Bocci
Summary: This study investigates the role of MC4R in melanoma and the use of the selective antagonist ML in combination with vemurafenib. The results show that ML can inhibit melanoma cell proliferation and induce apoptosis through the inhibition of ERK1/2 phosphorylation and reduction of BCL-XL expression. The combination of vemurafenib and ML exhibits a synergistic effect in vitro and inhibits tumor growth in vivo without causing adverse effects.
BIOCHEMICAL PHARMACOLOGY
(2024)
Article
Pharmacology & Pharmacy
Conor J. Bloxham, Katina D. Hulme, Fabrizio Fierro, Christian Fercher, Cassandra L. Pegg, Shannon L. O'Brien, Simon R. Foster, Kirsty R. Short, Sebastian G. B. Furness, Melissa E. Reichelt, Masha Y. Niv, Walter G. Thomas
Summary: Bitter taste receptors (T2Rs) are a type of G protein-coupled receptors that allow humans to detect aversive and toxic substances. This study characterized the functional properties of previously identified T2Rs in human cardiac tissues and their naturally occurring polymorphisms. The results showed differences in signaling among different T2R variants, and revealed a potential association between the T2R50 Tyr203 variant and cardiovascular disease.
BIOCHEMICAL PHARMACOLOGY
(2024)
Article
Pharmacology & Pharmacy
Lu Chen, Huanying Shi, Wenxin Zhang, Yongjun Zhu, Haifei Chen, Zimei Wu, Huijie Qi, Jiafeng Liu, Mingkang Zhong, Xiaojin Shi, Tianxiao Wang, Qunyi Li
Summary: This study demonstrates that Carfilzomib exhibits potent anti-tumor activity against esophageal squamous cell carcinoma (ESCC) by triggering mitochondrial apoptosis and reprogramming cellular metabolism. It has been identified that activating transcription factor 3 (ATF3) plays a crucial role as a cellular target in ESCC cells treated with Carfilzomib. Overexpression of ATF3 effectively counteracts the effects of Carfilzomib on ESCC cell proliferation, apoptosis, and metabolic reprogramming. Furthermore, ATF3 mediates the anti-tumor activity of Carfilzomib, suggesting its potential as a therapeutic agent for ESCC.
BIOCHEMICAL PHARMACOLOGY
(2024)
Review
Pharmacology & Pharmacy
Xing Zhang, Xiang Li, Ran Xia, Hong-Sheng Zhang
Summary: This review summarizes recent progress on the mechanisms of ferroptosis resistance in cancer and highlights the role of redox status and metabolism. Combination therapy for ferroptosis has great potential in treating resistant malignant tumors.
BIOCHEMICAL PHARMACOLOGY
(2024)