Article
Multidisciplinary Sciences
Dinh Hoa Hoang, Dandan Zhao, Sergio Branciamore, Davide Maestrini, Ivan R. Rodriguez, Ya-Huei Kuo, Russell Rockne, Samer K. Khaled, Bin Zhang, Le Xuan Truong Nguyen, Guido Marcucci
Summary: In acute myeloid leukemia (AML), FLT3-ITD regulates the biogenesis of miR-126 and miR-155. FLT3-ITD induces the expression of miR-155, which down-regulates SHIP1 and increases AKT activity, leading to increased cell cycle progression. Additionally, miR-155 down-regulates SPRED1 and blocks the biogenesis of miR-126, resulting in decreased levels of mature miR-126.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Letter
Oncology
Peihong Wang, Xinhua Xiao, Yuyin Zhang, Baoyuan Zhang, Donghe Li, Mingzhu Liu, Xi Xie, Chenxuan Liu, Ping Liu, Ruibao Ren
Summary: Research has identified KX2-391 as a promising FLT3 inhibitor for treating AML patients, especially those with drug-resistant FLT3-ITD-TKD mutations, showing significant efficacy in inhibiting FLT3 phosphorylation and enhancing apoptosis in AML cell lines.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2021)
Article
Oncology
Corinna Spohr, Teresa Poggio, Geoffroy Andrieux, Katharina Schoenberger, Nina Cabezas-Wallscheid, Melanie Boerries, Sebastian Halbach, Anna L. Illert, Tilman Brummer
Summary: The presence of internal tandem duplications (ITD) in FMS-like tyrosine kinase 3 (FLT3) combined with DNMT3A mutations in acute myeloid leukemia (AML) leads to poor prognosis. Studies have shown that GAB2 is essential for the development of Flt3-ITD driven AML, with Gab2 deficient mice displaying prolonged survival and reduced pathology. Gab2 increases signaling of receptor tyrosine kinases, promoting AML aggressiveness and drug resistance, making it a promising biomarker and therapeutic target in human AML.
Article
Medicine, Research & Experimental
Dan Xu, Yishan Chen, Ying Yang, Zhao Yin, Changfen Huang, Qiang Wang, Ling Jiang, Xuejie Jiang, Changxin Yin, Qifa Liu, Guopan Yu
Summary: Autophagy plays a critical role in drug resistance in FLT3-ITD-positive AML. It can be activated by acquired mutation or bone marrow micro-environment (BME) and mediates resistance to FLT3 inhibitors. Inhibiting autophagy could be a promising strategy to overcome resistance.
JOURNAL OF TRANSLATIONAL MEDICINE
(2022)
Article
Pharmacology & Pharmacy
Fangfang Wang, Jingcao Huang, Tingting Guo, Yuhuan Zheng, Li Zhang, Dan Zhang, Fujue Wang, Duolan Naren, Yushan Cui, Xiaoyan Liu, Ying Qu, Hongmei Luo, Yan Yang, Haichen Wei, Yong Guo
Summary: The combination treatment of HHT with quizartinib has shown synergistic effects on inhibiting cell growth, inducing apoptosis, and prolonging survival in mice with FLT3-ITD AML, suggesting it as a promising therapeutic strategy.
BIOCHEMICAL PHARMACOLOGY
(2021)
Article
Hematology
Shota Yokoyama, Masahiro Onozawa, Shota Yoshida, Naoki Miyashita, Hiroyuki Kimura, Shogo Takahashi, Toshihiro Matsukawa, Hideki Goto, Shinichi Fujisawa, Kosuke Miki, Daisuke Hidaka, Junichi Hashiguchi, Kentaro Wakasa, Makoto Ibata, Yukari Takeda, Akio Shigematsu, Katsuya Fujimoto, Yutaka Tsutsumi, Akio Mori, Toshimichi Ishihara, Yasutaka Kakinoki, Takeshi Kondo, Daigo Hashimoto, Takanori Teshima
Summary: Recent advances in next-generation sequencing have allowed for the detection of subclinical minute FLT3-ITD. We found that the molecular characteristics of minute FLT3-ITD were similar to clinically relevant FLT3-ITD, and the relapse rate was significantly higher in cases with minute FLT3-ITD. We observed the expansion of minute FLT3-ITD to become a dominant clone at relapse in clinically FLT3-ITD-negative AML.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Multidisciplinary Sciences
Kun-Yin Qiu, Xiong-Yu Liao, Yong Liu, Ke Huang, Yang Li, Jian-Pei Fang, Dun-Hua Zhou
Summary: This study explores the relationship between FLT3/ITD allelic ratio and prognosis in pediatric AML patients and identifies an optimal threshold value, highlighting the importance of individualized treatment for pediatric AML.
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Stefan Bjelosevic, Emily Gruber, Andrea Newbold, Carolyn Shembrey, Jennifer R. Devlin, Simon J. Hogg, Lev Kats, Izabela Todorovski, Zheng Fan, Thomas C. Abrehart, Giovanna Pomilio, Andrew Wei, Gareth P. Gregory, Stephin J. Vervoort, Kristin K. Brown, Ricky W. Johnstone
Summary: FLT3-ITD promotes serine synthesis in AML, making FLT3-ITD-driven leukemias dependent on serine for proliferation and survival. Pharmacologically exploiting this metabolic dependency can sensitize FLT3-ITD-driven AML to chemotherapy.
Article
Medicine, Research & Experimental
Ying Xu, Ping Wang, Mengyuan Li, Zhaoxing Wu, Xian Li, Jianping Shen, Rongzhen Xu
Summary: Triptonide is a natural small molecule that can efficiently inhibit FLT3-ITD-driven AML in vitro and in vivo, targeting the Hedgehog/FLT3 signaling pathway. This study identifies Hedgehog/FLT3 axis as a novel target for treating FLT3-ITD-driven leukemia and demonstrates that triptonide is an active lead compound with good efficacy and tolerability for killing FLT3-ITD-driven leukemia cells.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Oncology
Xinhua Xiao, Peihong Wang, Weina Zhang, Jiayi Wang, Mansi Cai, Hua Jiang, Yingli Wu, Huizhuang Shan
Summary: Our study revealed that GNF-7 is a potent FLT3-ITD inhibitor, exhibiting strong anti-leukemia activity against primary FLT3-ITD AML samples. GNF-7 binds to FLT3 protein and inhibits downstream signaling pathways, including STAT5, PI3K/AKT, and MAPK/ERK. It also shows potent inhibitory activity against FLT3-ITD/F691L that confers resistance to quizartinib or gilteritinib. Additionally, GNF-7 exhibits cytotoxic effect on leukemic stem cells, significantly extends survival in a PDX model, and shows comparable therapeutic effects to gilteritinib.
CANCER CELL INTERNATIONAL
(2023)
Article
Health Care Sciences & Services
David J. Wooten, Melat Gebru, Hong-Gang Wang, Reka Albert
Summary: The study investigated the gene expression changes in FLT3-mutant AML cell lines in response to drug treatment, identifying seven gene programs involved in AML drug-induced changes. By constructing a network of FLT3-ITD AML and applying the BooleaBayes algorithm, a probabilistic, data-driven dynamical model of acquired resistance to drugs was created, revealing potential interventions to disrupt the drug response system and prevent resistance.
JOURNAL OF PERSONALIZED MEDICINE
(2021)
Article
Oncology
Jong-Mi Lee, Silvia Park, Insik Hwang, Dain Kang, Byung Sik Cho, Hee-Je Kim, Ari Ahn, Myungshin Kim, Yonggoo Kim
Summary: This article presents an ITD-tracing algorithm based on NGS method for monitoring MRD in AML patients. The assay shows high sensitivity and superior performance, and demonstrates prognostic value in AML patients undergoing allogeneic hematopoietic stem cell transplantation.
Review
Oncology
Tobias R. Haage, Burkhart Schraven, Dimitrios Mougiakakos, Thomas Fischer
Summary: Mutations of the FLT3 gene are common in AML, occurring as internal tandem duplications (FLT3-ITD) in approximately 30% of cases. The specific insertion sites of FLT3-ITD show significant heterogeneity in biological and clinical features. Non-juxtamembrane domain (non-JMD) FLT3-ITD insertions have been associated with worse clinical outcomes and resistance to treatment. This review highlights the importance of considering non-JMD FLT3-ITD mutations in risk stratification and developing targeted therapies for AML.
Article
Oncology
Javier Bregante, Anna Schoenbichler, Daniel Poeloeske, Lina Degenfeld-Schonburg, Garazi Monzo Contreras, Emir Hadzijusufovic, Elvin D. de Araujo, Peter Valent, Richard Moriggl, Anna Orlova
Summary: FLT3-ITD mutations are common and detrimental in AML, with AML cells quickly developing resistance to FLT3 kinase inhibitors. Through a drug screen, new potential therapeutics like ispinesib, WS6, ponatinib, and cabozantinib have been identified for FLT3-ITD+ AML. Combination therapy with cabozantinib and ispinesib shows strong efficacy against FLT3-ITD+ AML, suggesting promising novel treatment options for this clinical challenge.
Article
Oncology
Yu Qian, Xiang Zhang, Shihui Mao, Wenwen Wei, Xiangjie Lin, Qing Ling, Wenle Ye, Fenglin Li, Jiajia Pan, Yutong Zhou, Yanchun Zhao, Xin Huang, Jiansong Huang, Hongyan Tong, Jie Sun, Jie Jin
Summary: In this study, the synergistic lethal effects of a novel BRD4 inhibitor (ACC010) and HHT in treating AML were explored. The co-treatment of ACC010 and HHT showed synergistic inhibition of cell proliferation, induction of apoptosis, and cell cycle arrest in FLT3-ITD-positive AML cells in vitro, as well as significant inhibition of AML progression in vivo. These findings suggest that the combination treatment of ACC010 and HHT could be a promising strategy for AML patients, particularly those with FLT3-ITD.
MOLECULAR ONCOLOGY
(2023)
Article
Oncology
Kuo-Hsing Chen, Chia-Lang Hsu, Yu-Li Su, Chang-Tsu Yuan, Liang-In Lin, Jia-Huei Tsai, Yi-Hsin Liang, Ann-Lii Cheng, Kun-Huei Yeh
Summary: This study found that the immune contexture in the tumor microenvironment is closely associated with prognosis in patients with metastatic BRAF V600E mutant colorectal cancer. High expression of immune genes and complement activation are correlated with poor prognosis, and the complement score is strongly correlated with tumor-associated macrophage M2 signatures.
BRITISH JOURNAL OF CANCER
(2023)
Article
Medicine, General & Internal
Chi-Yuan Yao, Chien-Chin Lin, Yu-Hung Wang, Chia-Lang Hsu, Chein-Jun Kao, Hsin-An Hou, Wen-Chien Chou, Hwei-Fang Tien
Summary: This study reveals that high expression of S100A4 gene is associated with clinical features, mutations, and transcriptomic profiles in acute myeloid leukemia (AML) patients. The higher expression level of S100A4 is correlated with poor prognosis, indicating its potential as a prognostic biomarker and a guide for treatment planning in AML.
JOURNAL OF THE FORMOSAN MEDICAL ASSOCIATION
(2023)
Article
Medicine, General & Internal
Li-Nien Chien, Huey-En Tzeng, Hung-Yi Liu, Wen-Chien Chou, Hwei-Fang Tien, Hsin-An Hou
Summary: This retrospective cohort study analyzed a comprehensive population-based database in Taiwan from 2001 to 2015 to provide detailed information on patients with acute myeloid leukemia (AML). Results showed that AML is the most common acute leukemia in adults with high mortality. Factors such as age, sex, year of diagnosis, socio-economic status, and hospital level were associated with survival.
JOURNAL OF THE FORMOSAN MEDICAL ASSOCIATION
(2023)
Letter
Hematology
Yu-Hung Wang, Chien-Chin Lin, Chi-Yuan Yao, Fabio M. R. Amaral, Shan-Chi Yu, Chein-Jun Kao, Pin-Tsen Shih, Hsin-An Hou, Wen-Chien Chou, Hwei-Fang Tien
Article
Hematology
Min-Yen Lo, Xavier Cheng-Hong Tsai, Chien-Chin Lin, Feng-Ming Tien, Yuan-Yeh Kuo, Wan-Hsuan Lee, Yen-Ling Peng, Ming-Chih Liu, Mei-Hsuan Tseng, Cheng-An Hsu, Jui-Che Chen, Liang-In Lin, Hsun- Sun, Yi-Kuang Chuang, Bor-Sheng Ko, Jih-Luh Tang, Ming Yao, Wen-Chien Chou, Hsin-An Hou, Hwei-Fang Tien
Summary: The European LeukemiaNet (ELN) proposed a revised recommendation, ELN-2022, for the diagnosis and management of acute myeloid leukemia (AML) in adults. This study aimed to validate the prognostic relevance of ELN-2022 in a cohort of younger AML patients. The results showed that ELN-2022 effectively distinguished patients with different risk groups and could be further refined for better risk stratification among AML patients. Prospective validation of the new predictive model is necessary.
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Grace A. Ward, Robert P. P. Dalton III, Benjamin S. Meyer, Amy F. McLemore, Amy L. Aldrich, Nghi B. Lam, Alexis H. Onimus, Nicole D. Vincelette, Thu Le Trinh, Xianghong Chen, Alexandra R. Calescibetta, Sean M. Christiansen, Hsin-An Hou, Joseph O. Johnson, Kenneth L. Wright, Eric Padron, Erika A. Eksioglu, Alan F. List
Summary: Myelodysplastic Syndromes (MDSs) are characterized by innate immune activation and pyroptotic cell death driven by NLRP3 inflammasome. The release of oxidized mitochondrial DNA (ox-mtDNA) into the cytosol enhances the inflammatory response in healthy tissues via engagement with Toll-like receptor 9 (TLR9). Blocking the TLR9/ox-mtDNA axis may be a promising therapeutic strategy for MDS.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Immunology
Shan-Wen Lui, Ting-Yu Hsieh, Jeng-Wei Lu, Yen-Chen Chen, Ting-Chun Lin, Yi-Jung Ho, Feng-Cheng Liu
Summary: This study found that JAKi mainly inhibits Fas+ T cell subsets, and the percentage changes in Th Fas+ cells and Naive Th Fas+ cells are positively correlated with the Disease Activity Score in RA patients. A prediction index was developed to assess the efficacy of JAKi prior to treatment. These findings contribute to the development of personalized treatment strategies for RA patients.
Article
Biotechnology & Applied Microbiology
Chi-Yang Tseng, Yu-Hsuan Fu, Da-Liang Ou, Jeng-Wei Lu, Hsin-An Hou, Liang-In Lin
Summary: Omipalisib exhibits anti-tumor effects in acute myeloid leukemia (AML) cells by inhibiting PI3K/AKT/mTOR signaling, suppressing mitochondrial respiration and biogenesis, and modulating metabolite levels.
CANCER GENE THERAPY
(2023)
Article
Biochemistry & Molecular Biology
Pei-Yi Chen, Ching-Yen Lin, Chia-Ling Wu, Pei Ying Keak, Je-Wen Liou, Wan-Yun Gao, Liang-In Lin, Jui-Hung Yen
Summary: This study investigates the antileukemic effects of pinostrobin, a flavonoid phytochemical, in human acute myeloid leukemia (AML) cells. Pinostrobin significantly reduces the viability of AML cells and suppresses cell proliferation, modulates cell cycle progression, promotes cell apoptosis, and induces monocytic differentiation. Pinostrobin also increases the expression of the tumor suppressor FOXO3 and inhibits cell growth. Furthermore, pinostrobin synergistically reduces the viability of AML cells when combined with cytarabine. These findings highlight pinostrobin's potential as a chemotherapeutic agent or nutraceutical supplement for AML prevention or treatment.
CHEMICO-BIOLOGICAL INTERACTIONS
(2023)
Article
Chemistry, Medicinal
Jeng-Wei Lu, Chin-Kai Huang, Yen-Chen Chen, Guan-Chiun Lee, Yi-Jung Ho
Summary: Dengue fever is an acute febrile disease caused by dengue virus (DENV) infection, and currently there are no effective drugs for clinical treatment. This study found that TML can inhibit DENV infection by restricting viral binding, entry, replication, and release. The results suggest that TML has the potential to be developed as a drug for treating dengue virus infection.
DRUG DEVELOPMENT RESEARCH
(2023)
Article
Food Science & Technology
Jiunn-Jye Chuu, Jeng-Wei Lu, Hung-Ju Chang, You-Hsiang Chu, Yi-Jen Peng, Yi-Jung Ho, Pei-Hung Shen, Yu-Shuan Chen, Chia-Hui Chen, Yi-Chien Liu, Chih-Chien Wang
Summary: Collagen peptides extracted from milkfish scales may serve as potential therapeutic candidates for osteoporosis by inhibiting osteoclast differentiation, promoting osteoblast proliferation, and potentially inhibiting bone density loss.
FOOD SCIENCE & NUTRITION
(2023)
Review
Oncology
Xinru Zhou, Yin Jia, Chuanbin Mao, Shanrong Liu
Summary: Small extracellular vesicles (sEVs), such as exosomes, have emerged as crucial targets for liquid biopsy and promising drug delivery vehicles in tumor progression. They can serve as biomarkers for tumor diagnosis and as drug carriers for cancer treatment.
Article
Oncology
Ruochan Chen, Ju Zhu, Xiao Zhong, Jie Li, Rui Kang, Daolin Tang
Summary: The interplay between autophagy and apoptosis plays a crucial role in tumorigenesis and cancer therapy, with HMGB1 serving as a key regulator in these processes.
Article
Oncology
Zongfu Pan, Xixuan Lu, Tong Xu, Jinming Chen, Lisha Bao, Ying Li, Yingying Gong, Yulu Che, Xiaozhou Zou, Zhuo Tan, Ping Huang, Minghua Ge
Summary: This study uncovered the emerging role of HN1 in promoting dedifferentiation of anaplastic thyroid cancer (ATC) cells. HN1 negatively regulated the thyroid differentiation markers and had an inhibitory effect on the transcriptional activation of CTCF, thereby influencing the chromatin accessibility of thyroid differentiation genes.
Article
Oncology
Yi Qin, Shengjun Xiong, Jun Ren, Gautam Sethi
Summary: Autophagy plays an important regulatory role in glioblastoma, and its dysregulation can lead to drug resistance and radioresistance. It also affects stem cell characteristics, overall growth, and metastasis. Therefore, autophagy is a promising target for glioblastoma therapy.
Article
Oncology
Katsuya Nagaoka, Xuewei Bai, Dan Liu, Kevin Cao, Joud Mulla, Chengcheng Ji, Hongze Chen, Muhammad Azhar Nisar, Amalia Bay, William Mueller, Grace Hildebrand, Jin-Song Gao, Shaolei Lu, Hiroko Setoyama, Yasuhito Tanaka, Jack R. Wands, Chiung-Kuei Huang
Summary: This study found that serum 2-OG levels in cholangiocarcinoma patients are associated with the effectiveness of chemotherapy. Patients with progressive disease showed significantly higher levels of serum 2-OG compared to stable disease and partial response patients. The study also revealed that overexpression of ASPH mimics the effects of 2-OG, and knockdown of ASPH improves chemotherapy. Targeting ASPH enhances the effects of chemotherapy by modulating ATM and ATR, two key regulators of DDRs.
