Article
Oncology
Hao Lu, Xiang-qin Weng, Yan Sheng, Jing Wu, Hui-min Xi, Xun Cai
Summary: Midostaurin combined with ATRA shows antitumor activity against AML with wild-type FLT3 mutations in vitro and in vivo. These findings may provide novel therapeutic strategies for some AML patients without FLT3 mutations and imply a new target of midostaurin.
Article
Oncology
Hui-Min Xi, Hao Lu, Xiang-Qin Weng, Yan Sheng, Jing Wu, Lu Li, Xun Cai
Summary: This study investigated the effect of the combination of salinomycin and ATRA on non-APL AML cells. The results showed that the combination treatment induced differentiation and apoptosis in AML cells by inhibiting the WNT/beta-catenin pathway and activating C/EBPs and PU.1. This study provides a novel therapeutic strategy for AML patients by targeting the WNT/beta-catenin pathway.
ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY
(2023)
Article
Oncology
Marie Sabatier, Emeline Boet, Sonia Zaghdoudi, Nathan Guiraud, Alexis Hucteau, Nathaniel Polley, Guillaume Cognet, Estelle Saland, Laura Lauture, Thomas Farge, Ambrine Sahal, Vera Pancaldi, Emeline Chu-Van, Florence Castelli, Sarah Bertoli, Pierre Bories, Christian Recher, Helena Boutzen, Veronique Mansat-De Mas, Lucille Stuani, Jean-Emmanuel Sarry
Summary: Around 15% of AML patients have mutations in IDH genes, leading to the production of the oncometabolite 2-HG. While inhibitors of mutant IDH enzymes have been approved, many patients do not respond due to mechanisms of resistance such as 2-HG rebound. This study shows that 2-HG activates VDR in IDH mutant AML cells, increasing sensitivity to vitamin D and ATRA combination therapy, offering a new approach for treating AML patients in this subgroup.
Article
Oncology
Luciana Yamamoto de Almeida, Diego A. Pereira-Martins, Isabel Weinhaeuser, Cesar Ortiz, Larissa A. Candido, Ana Paula Lange, Nayara F. De Abreu, Silvia E. S. Mendonza, Virginia M. de Deus Wagatsuma, Mariane C. Do Nascimento, Helder H. Paiva, Raquel M. Alves-Paiva, Camila C. O. M. Bonaldo, Daniele C. Nascimento, Jose C. Alves-Filho, Priscila S. Scheucher, Ana Silvia G. Lima, Jan Jacob Schuringa, Emanuele Ammantuna, Tiziana Ottone, Nelida I. Noguera, Cleide L. Araujo, Eduardo M. Rego
Summary: This study revealed that the EGFR pathway is active in APL patients, and the use of EGFR inhibitors can promote differentiation of APL cells, providing a potential strategy to alleviate resistance to ATRA and ATO.
FRONTIERS IN ONCOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Hanane Djamai, Jeannig Berrou, Melanie Dupont, Marie-Magdelaine Coude, Marc Delord, Emmanuelle Clappier, Alice Marceau-Renaut, Anna Kaci, Emmanuel Raffoux, Raphael Itzykson, Caroline Berthier, Hsin-Chieh Wu, Rita Hleihel, Ali Bazarbachi, Hugues de The, Andre Baruchel, Claude Gardin, Herve Dombret, Thorsten Braun
Summary: Studies have shown that BETi, like ATO + ATRA, induce differentiation and apoptosis in NPM1c AML cells independently of TP53; BETi induces differentiation through NPM1c degradation and maintains NPM1/BRD4 equilibrium in the nucleus; While ATO + ATRA demonstrates significant biological activity in NPM1c IMS-M2 cell line, those cells are resistant to BETi.
Article
Chemistry, Medicinal
Hui He, Chengqiang Wang, Gen Liu, Haoyue Ma, Mingdong Jiang, Pan Li, Qianwei Lu, Li Li, Hongyi Qi
Summary: The study demonstrates that Isobavachalcone induces apoptosis and differentiation of acute myeloid leukemia cells through multiple pathways, with the ROS-mediated signaling pathway playing a key role.
PHYTOTHERAPY RESEARCH
(2021)
Article
Pharmacology & Pharmacy
Maria Franza, Jacopo Albanesi, Benedetta Mancini, Rosa Pennisi, Stefano Leone, Filippo Acconcia, Fabrizio Bianchi, Alessandra di Masi
Summary: This study investigates the effects of MK-8776, a specific inhibitor of CHK1, on ATRA-resistant APL cells. Treatment with MK-8776 induces degradation of PML-RARa, increased expression of CD11b, and differentiation of APL cells. Combining MK-8776 with ATO shows a synergistic effect. This study suggests that MK-8776 could be a potential therapeutic option for APL patients resistant to standard ATRA/ATO therapy.
BIOCHEMICAL PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Fahui Li, Congying Gao, Xueming Li, Jiangyun Wang, Yao Zhao, Yu Ke, Ying Liu, Hong-Min Liu, Zhenbo Hu, Liuya Wei, Zhe-Sheng Chen
Summary: The natural compound Jiyuan oridonin A (JOA) has been found to overcome the differentiation blockade in AML cells and leukemic stem-like cells, inhibiting their proliferation and offering a novel therapeutic strategy for AML.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Oncology
Tatsuya Morishima, Koichi Takahashi, Desmond Wai Loon Chin, Yuxin Wang, Kenji Tokunaga, Yuichiro Arima, Masao Matsuoka, Toshio Suda, Hitoshi Takizawa
Summary: Genetic mutations in the IDH gene can result in the production of oncometabolite, which is associated with acute myeloid leukemia (AML). Although targeted inhibitors have been developed, refractoriness and resistance are still observed. This study found that aberrant metabolism in IDH mutant cells can persist even after normalization of oncometabolite level. Two signaling pathways, STAT phosphorylation and phospholipid metabolic adaptation, were identified to be important for the growth advantage of IDH2 mutant cells. The release of metabolic adaptation by anti-inflammatory drugs targeting arachidonic acid metabolism sensitized IDH2 mutant cells to apoptosis. These findings have implications for the development of alternative treatments for IDH2 mutant AML patients.
Article
Pharmacology & Pharmacy
Zhe Huang, Yan Yang, Xianming Fan, Wenzhe Ma
Summary: In this study, the pharmacological mechanisms of scutellarin for acute myeloid leukemia treatment were identified using network pharmacology and experimental validation. The results revealed the importance of the JNK pathway in scutellarin-mediated AML treatment.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Immunology
Lucille Stuani, Marie Sabatier, Estelle Saland, Guillaume Cognet, Nathalie Poupin, Claudie Bosc, Florence A. Castelli, Lara Gales, Evgenia Turtoi, Camille Montersino, Thomas Farge, Emeline Boet, Nicolas Broin, Clement Larrue, Natalia Baran, Madi Y. Cisse, Marc Conti, Sylvain Loric, Tony Kaoma, Alexis Hucteau, Aliki Zavoriti, Ambrine Sahal, Pierre-Luc Mouchel, Mathilde Gotanegre, Cedric Cassan, Laurent Fernando, Feng Wang, Mohsen Hosseini, Emeline Chu-Van, Laurent Le Cam, Martin Carroll, Mary A. Selak, Norbert Vey, Remy Castellano, Francois Fenaille, Andrei Turtoi, Guillaume Cazals, Pierre Bories, Yves Gibon, Brandon Nicolay, Sebastien Ronseaux, Joseph R. Marszalek, Koichi Takahashi, Courtney D. DiNardo, Marina Konopleva, Vera Pancaldi, Yves Collette, Floriant Bellvert, Fabien Jourdan, Laetitia K. Linares, Christian Recher, Jean-Charles Portais, Jean-Emmanuel Sarry
Summary: Mutations in IDH lead to enhanced mitochondrial oxidative metabolism in AML, involving increased electron transport chain activity and fatty acid oxidation. IDH1 mutant inhibitors reduce 2-HG levels and CEBPα methylation, but do not reverse fatty acid oxidation and OxPHOS. Targeting mitochondrial activities may improve anti-AML efficacy of IDH mutant inhibitors.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Article
Oncology
Junmei Zhao, Wentao Wang, Li Yan, Xi Chen, Wen Li, Wanying Li, Tingting Chen, Lunhua Chen
Summary: Rearrangement of the retinoic acid receptor gamma (RARG) gene is a common occurrence in acute myeloid leukemia (AML) patients, resembling classical acute promyelocytic leukemia (APL) patients. However, they do not carry the promyelocytic leukemia (PML)-RARA fusion gene. These APL-like AML patients are typically resistant to all-trans retinoic acid (ATRA) and currently have no effective treatment options. This study identified a rare cleavage and polyadenylation-specific factor 6 (CPSF6)-RARG fusion gene in an AML case resembling APL. The patient showed insensitivity to ATRA and ATO but responded well to homoharringtonine and cytarabine.
FRONTIERS IN ONCOLOGY
(2022)
Review
Oncology
Karina Barbosa, Aniruddha J. Deshpande
Summary: One important property of hematopoietic stem cells is their ability to self-renew, which is often exploited in blood cancers. Acute myeloid leukemia (AML) follows a hierarchical arrangement with self-renewing leukemia stem cells (LSCs) giving rise to the bulk of the tumor. LSCs have been found to be responsible for chemotherapy resistance and serve as a reservoir for disease relapse. Understanding the characteristics of LSCs compared to normal stem cells has opened up opportunities for targeted therapies in AML.
FRONTIERS IN ONCOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Bo Dai, Feng Wang, Ying Wang, Jiayan Zhu, Yunxuan Li, Tingting Zhang, Luyao Zhao, Lining Wang, Wenhui Gao, Junmin Li, Honghu Zhu, Ke Li, Jiong Hu
Summary: Acute promyelocytic leukemia (APL) is driven by PML-RAR alpha oncoprotein, which is suppressed by HDAC3 inhibition to reduce the expression of PML-RAR alpha and induce differentiation, apoptosis, and decreased self-renewal of APL cells. HDAC3 deacetylates PML-RAR alpha, reducing its SUMOylation and subsequent ubiquitylation. Inhibiting HDAC3 with drugs or genetic methods shows promise as a strategy to treat relapsed/refractory APL.
CELL DEATH AND DIFFERENTIATION
(2023)
Article
Biochemistry & Molecular Biology
Jing Zhou, Xing Chen, Pan Zhou, Xiaolu Sun, Yangpeng Chen, Mengke Li, Yajing Chu, Jianfeng Zhou, Xuelian Hu, Yi Luo, Weiping Yuan, Gaoxiang Wang
Summary: This study reveals the crucial role of osteopontin (OPN) in acute myeloid leukemia (AML), showing that OPN contributes to the maintenance of leukemia stem cells (LSCs) by preventing apoptosis and cell cycle arrest. Therefore, OPN could be a potential therapeutic target for AML treatment.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
