Review
Hematology
Amir T. Fathi, Eytan M. Stein, Courtney D. DiNardo, Mark J. Levis, Pau Montesinos, Stephane de Botton
Summary: Differentiation Syndrome (DS), identified in some AML patients treated with novel differentiation therapies like IDH and FLT3 inhibitors, is a well-known complication in APL but efforts are ongoing to standardize its diagnosis and treatment in AML. While the rates vary, many signs and symptoms are common between APL and AML, and although DS can lead to fatal complications, prompt management is usually effective and rarely requires interrupting AML therapy.
AMERICAN JOURNAL OF HEMATOLOGY
(2021)
Article
Chemistry, Medicinal
Yuqi Jiang, Jie Xu, Kairui Yue, Chao Huang, Mengting Qin, Dongyu Chi, Qixin Yu, Yue Zhu, Xiaohan Hou, Tongqiang Xu, Min Li, C. James Chou, Xiaoyang Li
Summary: The study focused on modifying HDAC inhibitors to deactivate the Michael reaction in order to improve their potency. Compound 11h showed significant improvements in both HDAC inhibitory activity and cell-based antitumor assay, demonstrating potential for clinical application and efficacy against AML.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Editorial Material
Cell & Tissue Engineering
Malini Gupta, Britta Will
Summary: Adaptive aberrant gene regulation is a hallmark of malignant growth and therapy resistance in acute myeloid leukemia (AML). In this study, Eagle et al. identified oncogenic enhancer-driven overexpression of selenophosphate synthetase 2 (SEPHS2) as a targeted opportunity for mitigating malignant cell growth in AML.
Review
Biochemistry & Molecular Biology
Rikako Tabata, SungGi Chi, Junichiro Yuda, Yosuke Minami
Summary: Studies have suggested the potential clinical benefits of immuno-oncology therapy against AML, including immune checkpoint inhibitors and bi-/tri-specific antibodies. CAR-T and NK cells have shown effectiveness for relapsed/refractory AML patients, and conventional chemotherapy combined with anti-PD-1/anti-CTLA4 antibodies also demonstrated certain efficacy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Cell Biology
Grace Egan, Aaron D. Schimmer
Summary: Acute myeloid leukemia (AML), a malignant disease, is driven by somatic mutations. Unique mitochondrial and metabolic dependencies, including reliance on oxidative phosphorylation, have been identified in AML and AML stem cells. Metabolic enzymes have recently been found to play noncanonical roles in regulating gene expression, cell differentiation, and stemness in AML. These mitochondrial and metabolic adaptations are independent of underlying genomic abnormalities and contribute to chemoresistance and relapse.
TRENDS IN CELL BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Dade Rong, Xiaomin Chen, Jing Xiao, Daiyuan Liu, Xiangna Ni, Xiuzhen Tong, Haihe Wang
Summary: This study identified novel molecular subtypes of AML associated with histone methylation and established a scoring system to predict treatment response and prognosis. The M-RiskScore was found to be a useful prognostic biomarker and guide for the choice of appropriate chemotherapy strategy.
Article
Biochemistry & Molecular Biology
Stefan Nagel, Claudia Pommerenke, Corinna Meyer, Roderick A. F. MacLeod
Summary: Homeobox genes encode transcription factors that control basic developmental decisions, and their hematopoietic activities have implications for both normal and malignant immune cell development. By constructing lymphoid TALE-code and myeloid TALE-code, expression patterns of active TALE class homeobox genes in early hematopoiesis and lymphopoiesis were revealed, providing insights into the regulatory roles of these genes in AML and identifying potential oncogenic activities when deregulated. Further analysis of gene expression and knockout experiments in AML cell lines demonstrated the impact of IRX factors in normal and malignant myeloid differentiation, suggesting potential therapeutic targets for AML.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Pediatrics
Huan Xu, Yuxi Wen, Runming Jin, Hongbo Chen
Summary: This review discusses the genetic alterations and epigenetic dysregulations of hematopoietic progenitor cells in acute myeloid leukemia (AML), emphasizing the role of epigenetic abnormalities in leukemogenesis. The current progress in epigenetic targeted therapy and its potential value in precision and combinational therapy for pediatric AML are also described.
FRONTIERS IN PEDIATRICS
(2022)
Article
Oncology
Manman Wang, Hao Guo, Xuechun Zhang, Xiyang Wang, Hu Tao, Tan Zhang, Min Peng, Min Zhang, Zan Huang
Summary: Recent studies identified ANP32A as a novel biomarker of unfavorable outcome of leukemia, suggesting that targeting ANP32A may be a promising therapeutic strategy against AML. Disrupting ANP32A and H3 interaction with H3-binding peptide can impair the oncogenicity of ANP32A and potentially treat AML effectively.
TRANSLATIONAL ONCOLOGY
(2022)
Article
Nanoscience & Nanotechnology
Tao Wang, Xue Zhang, Mengfan Jia, Aiyun Yang, Jian Liu, Tao Wen, Jie Meng, Haiyan Xu
Summary: This study investigates the differentiation-induction effects of lab-developed hydrophilic nanocrystals of As4S4 (ee-As4S4) on acute myeloid leukemia (AML) cells. The results show that ee-As4S4 induces effective and multiple-lineage differentiation and apoptosis of AML cells in mouse models and cell lines. The inhibition of histone deacetylase activity plays an important role in the differentiation-induction effects. Furthermore, ee-As4S4 improves the survival of AML mice without causing acute or chronic toxicity in healthy mice, suggesting its promising potential as a novel inductive agent in differentiation therapy of AML.
INTERNATIONAL JOURNAL OF NANOMEDICINE
(2022)
Article
Oncology
Ipek Bulut, Adam Lee, Buse Cevatemre, Dusan Ruzic, Roman Belle, Akane Kawamura, Sheraz Gul, Katarina Nikolic, A. Ganesan, Ceyda Acilan
Summary: The newly developed LSD1/HDAC6 dual inhibitor iDual can inhibit the growth of leukemia cells by simultaneously targeting HDAC6 and LSD1, and it can enhance drug-induced apoptosis when used in combination with doxorubicin.
Review
Pharmacology & Pharmacy
Shujing Zhang, Menghan Liu, Yongfang Yao, Bin Yu, Hongmin Liu
Summary: Targeted therapy for AML focusing on LSD1 has shown effectiveness, with LSD1 inhibitors such as TCP, ORY-1001, GSK2879552, and IMG-7289 showing promise in clinical trials. Combination therapies with other drugs may enhance treatment outcomes.
PHARMACOLOGICAL RESEARCH
(2021)
Review
Biochemistry & Molecular Biology
Daniela Damiani, Mario Tiribelli
Summary: The prognosis of acute myeloid leukemia (AML) is poor due to tumor cell immune escape, which weakens T-cells. Inhibiting immune checkpoints (ICs) through immune checkpoint inhibitors (ICIs) has emerged as a promising therapeutic strategy for AML. However, the results of clinical trials testing ICIs, alone or in combination with other treatments, in AML are conflicting.
Article
Oncology
Jia Yin, Chao-Ling Wan, Ling Zhang, Hao Zhang, Lian Bai, Hai-Xia Zhou, Ming-Zhu Xu, Li-Yun Chen, Chong-Sheng Qian, Hui-Ying Qiu, Su-Ning Chen, Xiao-Wen Tang, De-Pei Wu, Yan-Ming Zhang, Ai-Ning Sun, Sheng-Li Xue
Summary: The study investigated the role of chidamide, decitabine plus priming regimen in the salvage treatment of relapsed/refractory acute myeloid leukemia. The CDIAG regimen showed good antileukemia activity in these patients with acceptable adverse events.
FRONTIERS IN ONCOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Vijendra Singh, Mohammed Hafiz Uddin, Jeffrey A. Zonder, Asfar S. Azmi, Suresh Kumar Balasubramanian
Summary: While mechanistic studies have shed light on the molecular mechanisms of AML and led to the development of new targeted therapies, resistance remains a significant issue in AML treatment. The exploration of circRNA in AML biology and therapy resistance shows promise in providing new insights and potential solutions to managing this disease.