Article
Biochemistry & Molecular Biology
Meng-Xi Wang, Li Yan, Juan Chen, Jun-Mei Zhao, Jiang Zhu, Shan-He Yu
Summary: This study explored the feasibility of reducing the malignant characteristics of t(8;21) AML cells by reinforcing their endogenous differentiation potential. The results showed that in an AE9a murine model, the process of erythroid differentiation was accompanied by a decline or loss of leukemia-initiating potential. Therefore, enhancing the erythroid differentiation of t(8;21) AML cells may be a promising intervention strategy.
Article
Oncology
Daniel T. Johnson, Amanda G. Davis, Jie-Hua Zhou, Edward D. Ball, Dong-Er Zhang
Summary: AML1-ETO is post-transcriptionally regulated by let-7b, which contributes to the leukemic phenotype of t(8;21) AML and may be important for t(8;21) leukemogenesis and maintenance. Let-7b microRNA directly represses AML1-ETO through a negative regulatory element within the AML1-ETO 3'UTR, inhibiting cell proliferation and promoting differentiation in t(8;21) AML cell lines.
EXPERIMENTAL HEMATOLOGY & ONCOLOGY
(2021)
Article
Multidisciplinary Sciences
Qian Chen, Murat A. Cevher, Qi Jiang, Saisai Wang, Xiaojian Sun, Robert G. Roeder, Mo Chen
Summary: The AML1-ETO fusion protein is a key factor in acute myeloid leukemia, with its activity dependent on the LYL1 component in the AETFC complex. Through interaction with CARM1, LYL1 facilitates the binding of AETFC to active enhancers, leading to the activation of AML1-ETO-dependent gene expression.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Chemistry, Multidisciplinary
Long Fang, Ruofei Zhang, Lin Shi, Jiaying Xie, Long Ma, Yili Yang, Xiyun Yan, Kelong Fan
Summary: The study demonstrates the potential therapeutic effect of protein-nanocaged selenium as an epigenetic regulator against t(8;21) leukemia.
Article
Biochemistry & Molecular Biology
Ying Wang, Yu Liu, Yingxi Xu, Haiyan Xing, Zheng Tian, Kejing Tang, Qing Rao, Min Wang, Jianxiang Wang
Summary: This study identifies several AML1-ETO-related fusion circular RNAs (F-CircAEs) and reveals that F-CircAEs can impact the growth of AML1-ETO leukemia cells by regulating the glycolysis pathway. This finding is significant in understanding the pathogenesis of AML1-ETO leukemia and providing new diagnostic markers and therapeutic targets.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Ze Chen, Yang-Liu Shao, Li-Li Wang, Ji Lin, Ji-Bin Zhang, Yi Ding, Bin-bin Gao, Dai-Hong Liu, Xiao-Ning Gao
Summary: YTHDF2 is highly expressed in t(8;21) AML patients, associated with a higher risk of relapse and inferior relapse-free survival. Knockdown of YTHDF2 impairs cell proliferation rate, possibly by modulating global m(6)A methylation to promote growth of t(8;21) AML cells.
Article
Oncology
Hasan Issa, Laura E. E. Swart, Milad Rasouli, Minoo Ashtiani, Sirintra Nakjang, Nidhi Jyotsana, Konstantin Schuschel, Michael Heuser, Helen Blair, Olaf Heidenreich
Summary: Hallmarks of AML include chromosomal rearrangements generating fusion genes, which are ideal therapeutic targets but difficult to treat conventionally. This study demonstrates the use of siRNA-loaded lipid nanoparticles to specifically target the leukaemic fusion gene RUNX1/ETO. Inhibition of RUNX1/ETO resulted in extended survival, reduced leukaemic proliferation, induced differentiation and impaired re-engraftment potential in vivo. These findings provide proof for targeting RUNX1/ETO and support further development of siRNA-LNPs for fusion gene-driven malignancies.
Article
Multidisciplinary Sciences
Vasily V. Grinev, Farnaz Barneh, Ilya M. Ilyushonak, Sirintra Nakjang, Job Smink, Anita van Oort, Richard Clough, Michael Seyani, Hesta McNeill, Mojgan Reza, Natalia Martinez-Soria, Salam A. Assi, Tatsiana V. Ramanouskaya, Constanze Bonifer, Olaf Heidenreich
Summary: The fusion oncogene RUNX1/RUNX1T1 plays a key role in acute myeloid leukemia by regulating alternative RNA splicing in leukemic cells. This regulation is achieved through changing 5'UTR structure, altering isoform expression, and controlling the expression of splicing factors. This study highlights the importance of alternative splicing in leukemia transcriptome re-organization by an aberrant transcriptional regulator.
NATURE COMMUNICATIONS
(2021)
Article
Biotechnology & Applied Microbiology
Kuan-Wei Su, Da-Liang Ou, Yu-Hsuan Fu, Hwei-Fang Tien, Hsin-An Hou, Liang-In Lin
Summary: Cabozantinib, an orally available multi-target tyrosine kinase inhibitor, showed potential therapeutic effects in an AML subtype characterized by t(8;21) and KIT mutation. It exerted cytotoxicity in Kasumi-1 cells, inhibited KIT phosphorylation and downstream signals, disrupted AML1-ETO fusion protein synthesis, suppressed tumorigenesis in a mouse model, and downregulated mTOR-mediated signaling pathways. Further clinical trials are warranted to evaluate its efficacy in AML treatment.
CANCER GENE THERAPY
(2022)
Article
Oncology
Zhiding Wang, Wei Guan, Mengzhen Wang, Jinghong Chen, Linlin Zhang, Yang Xiao, Lixin Wang, Yonghui Li, Li Yu
Summary: This study reveals a novel mechanism by which AML1-ETO can inhibit AML immune escape by regulating CD48 expression, providing new insights into the role of AML1-ETO and CD48 in AML. The findings suggest that AML patients with AML1-ETO oncogene infusion may have better clinical outcomes.
LEUKEMIA & LYMPHOMA
(2021)
Article
Cell Biology
Cheng-Long Hu, Bing-Yi Chen, Zijuan Li, Tianbiao Yang, Chun-Hui Xu, Ruirui Yang, Peng-Cheng Yu, Jingyao Zhao, Ting Liu, Na Liu, Bin Shan, Qunling Zhang, Junhong Song, Ming-Yue Fei, Li-Juan Zong, Jia-Ying Zhang, Ji-Chuan Wu, Shu-Bei Chen, Yong Wang, Binhe Chang, Dan Hou, Ping Liu, Yilun Jiang, Xiya Li, Xinchi Chen, Chu-Han Deng, Yi-Yi Ren, Roujia Wang, Jiacheng Jin, Kai Xue, Ying Zhang, Meirong Du, Jun Shi, Ling-Yun Wu, Chun-Kang Chang, Shuhong Shen, Zhu Chen, Sai-Juan Chen, Xiaolong Liu, Xiao-Jian Sun, Mingyue Zheng, Lan Wang
Summary: Aberrant expression of UHRF1, an epigenetic regulator, in acute myeloid leukemia (AML) is associated with poor prognosis. UHRF1 is crucial for the self-renewal of leukemia initiation cells (LICs) and its interaction with SAP30 represses gene expression. Inhibition of UHRF1 or SAP30 leads to derepression of MXD4, an MYC antagonist, and suppresses leukemogenesis. Furthermore, a UHRF1 inhibitor, UF146, shows promising therapeutic efficacy in a myeloid leukemia model.
Article
Oncology
Ming Yan, Mengdan Liu, Amanda G. Davis, Samuel A. Stoner, Dong-Er Zhang
Summary: By generating a moderate overexpression AML1-ETO9a knock-in mouse model, pre-leukemic alterations were observed in mice with AML1-ETO fusion oncoprotein, including skewing of progenitors towards granulocyte/monocyte lineages and replating of stem and progenitor cells. Single-cell RNA sequencing identified a subset of common myeloid progenitors with heightened granulocyte/monocyte bias in AE9a mice. Dysregulation of key hematopoietic transcription factor target gene networks and Sox4 activation were identified as potential contributors to stem cell self-renewal during the pre-leukemic stage.
Article
Cell Biology
Yi-Fan Zhang, Xiao-Lin Wang, Chun-Hui Xu, Na Liu, Ling Zhang, Yu-Ming Zhang, Yin-Yin Xie, Yuan-Liang Zhang, Qiu-Hua Huang, Lan Wang, Zhu Chen, Sai-Juan Chen, Robert G. Roeder, Shuhong Shen, Kai Xue, Xiao-Jian Sun
Summary: This study provides a comparative analysis of AML1-ETO and ETO2-GLIS2 fusion transcription factors in U937 leukemia cells. The study reveals that these fusion transcription factors share common DNA-binding domains and rely on cooperative transcription factors for binding. AML1-ETO can function as both a repressor and an activator, while ETO2-GLIS2 primarily acts as an activator. Additionally, the study highlights the differential regulation of key transcription factors involved in myeloid differentiation.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Cell Biology
Li Xia, Yue Jiang, Xue-Hong Zhang, Xin-Ran Wang, Ran Wei, Kang Qin, Ying Lu
Summary: The research demonstrates that SUMOylation of PKM2 plays a crucial role in blocking leukemia cell differentiation by triggering conformation change, reducing activity, and leading to nuclear translocation. Interaction between PKM2 and RUNX1 is shown to impact the differentiation status of the cells.
CELL DEATH & DISEASE
(2021)
Article
Oncology
Xiaoyan Chen, Suyu Zong, Meihui Yi, Chao Liu, Bingrui Wang, Yongjuan Duan, Xuelian Cheng, Min Ruan, Li Zhang, Yao Zou, Yumei Chen, Wenyu Yang, Ye Guo, Xiaojuan Chen, Tianyuan Hu, Tao Cheng, Xiaofan Zhu, Yingchi Zhang
Summary: Relapse of childhood AML1-ETO acute myeloid leukemia is often due to treatment failure, and optimized minimal residual disease monitoring methods are crucial in prevention. This study utilized next-generation sequencing and ddPCR for dynamic monitoring of AE-DNA, providing more sensitive quantitation and improved prognosis. The findings contribute valuable methods for dynamic surveillance of AE fusion DNA and prognosis determination.
TRANSLATIONAL ONCOLOGY
(2021)
Article
Hematology
Andrea Biondi, Valentino Conter, Mammen Chandy, Primus Ewald, Marie Lucia de Martino Lee, Vivek S. Radhakrishnan, Wannaphorn Rotchanapanya, Patricia Scanlan, Owen Patrick Smith, Boubacar Togo, Peter Hokland
Summary: As hematologists, the best treatment for patients with blood diseases may vary due to differing opinions and constraints, as well as differences in patient presentation and understanding worldwide. Patients in developed countries often present early and have a better understanding of their disease, impacting treatment management and outcomes.
BRITISH JOURNAL OF HAEMATOLOGY
(2022)
Article
Medical Laboratory Technology
Carina A. Rosenberg, Marie Bill, Orla Maguire, Marianne A. Petersen, Eigil Kjeldsen, Peter Hokland, Maja Ludvigsen
Summary: Studies have shown that T-cell acute lymphoblastic leukemia (T-ALL) blast populations may display immunophenotypic heterogeneity. The variation in expression of the blast marker TdT in T-ALL blasts corresponds to differences in morphometric features, and the imaging flow cytometry (IFC) allows for visual verification and improvement of applied gating strategies. The identification of TdT(neg) and TdT(pos) subpopulations in T-ALL blasts highlights the importance of phenotypic heterogeneity for delineation and quantification of blast subpopulations in the clinical setting.
CYTOMETRY PART B-CLINICAL CYTOMETRY
(2022)
Article
Oncology
Daniel T. Johnson, Jiarong Zhou, Ashley Kroll, Ronnie H. Fang, Ming Yan, Crystal Xiao, Xiufen Chen, Justin Kline, Liangfang Zhang, Dong-Er Zhang
Summary: AMCNP vaccine platform, coated with AML cell membrane material, enhances leukemia-specific antigen presentation and T cell responses, demonstrating promising therapeutic benefits against AML challenge and potentially preventing relapse after chemotherapy.
Editorial Material
Hematology
Ayalew Tefferi, Jean-Christophe Ianotto, Vikram Mathews, Jan Samuelsson, Natasha Szuber, Zhijian Xiao, Peter Hokland
BRITISH JOURNAL OF HAEMATOLOGY
(2022)
Article
Hematology
Stephane de Botton, Pau Montesinos, Andre C. Schuh, Cristina Papayannidis, Paresh Vyas, Andrew H. Wei, Hans Ommen, Sergey Semochkin, Hee-Je Kim, Richard A. Larson, Jaime Koprivnikar, Olga Frankfurt, Felicitas Thol, Joerg Chromik, Jenny Byrne, Arnaud Pigneux, Xavier Thomas, Olga Salamero, Maria Belen Vidriales, Vadim Doronin, Hartmut Doehner, Amir T. Fathi, Eric Laille, Xin Yu, Maroof Hasan, Patricia Martin-Regueira, Courtney D. DiNardo
Summary: This study compared the efficacy of the oral IDH2 inhibitor enasidenib with conventional care regimens (CCR) in older patients with late-stage mutant-IDH2 AML. Enasidenib significantly improved event-free survival, time to treatment failure, overall response rate, hematologic improvement, and transfusion independence compared to CCR. However, there was no significant difference in overall survival, possibly due to early dropout and subsequent AML-directed therapies.
Article
Hematology
Oliver Buchhave Pedersen, Erik Lerkevang Grove, Leonardo Pasalic, Hans Beier Ommen, Steen Dalby Kristensen, Anne-Mette Hvas
Summary: This study investigated the effects of cytoreductive treatment on platelet function and turnover in patients with essential thrombocythaemia. The results showed that different cytoreductive drugs may have varying impacts on platelet activity and turnover, which could help explain differences in the risk of thromboembolic events among these patients.
BRITISH JOURNAL OF HAEMATOLOGY
(2022)
Article
Hematology
Yi-Jou Huang, Jia-Yu Chen, Ming Yan, Amanda G. Davis, Sayuri Miyauchi, Liang Chen, Yajing Hao, Sigrid Katz, Rafael Bejar, Omar Abdel-Wahab, Xiang-Dong Fu, Dong-Er Zhang
Summary: This study presents a mouse model and a cellular model to demonstrate how alterations in transcription and splicing collectively contribute to the development of MDS in a double mutant.
Article
Oncology
Richard Dillon, Shanna Maycock, Aimee Jackson, Sonia Fox, Sylvie Freeman, Charles Craddock, Catherine Thomas, Emma Homer, Jane Leahy, Anna Mamwell, Nicola Potter, Nigel Russell, Andrew Wei, Hans Beier Ommen, Claire Hemmaway, Steve Knapper, Lucinda Billingham
Summary: The VICTOR trial is evaluating the non-inferiority of intensive chemotherapy and Venetoclax with low-dose cytarabine in older patients with AML. The trial employs an innovative Bayesian design and will expand to include younger patients if there is sufficient evidence of non-inferiority.
Article
Multidisciplinary Sciences
Kei-ichiro Arimoto, Sayuri Miyauchi, Ty D. Troutman, Yue Zhang, Mengdan Liu, Samuel A. Stoner, Amanda G. Davis, Jun-Bao Fan, Yi-Jou Huang, Ming Yan, Christopher K. Glass, Dong-Er Zhang
Summary: Immunotherapy is an effective cancer treatment, but not for all patients, prompting the need for alternative strategies. Inducing cancer immunogenic cell death (ICD) shows promise in promoting robust immune responses against tumor-associated antigens. Depletion of USP18, a negative regulator of interferon signaling, selectively induces ICD in cancer cells, suggesting targeting USP18 as a potential cancer immunotherapy.
NATURE COMMUNICATIONS
(2023)
Article
Hematology
Peter Hokland, Shahina Daar, Wael Khair, Sujit Sheth, Ali T. Taher, Lorenza Torti, Chattree Hantaweepant, Deborah Rund
Summary: The thalassaemias are a group of genetic disorders of haemoglobin found worldwide. Standard treatment involves regular transfusions and iron chelation therapy. Innovative therapies like bone marrow transplantation and gene therapy are not widely available. This article discusses the management strategies for a refugee patient with beta thalassaemia in six countries, highlighting the disparities in available therapies and the challenges of ensuring adherence to treatment.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Hematology
Peter Hokland, Isolda I. Fernandez, Sylvie D. Freeman, Bjorn T. Gjertsen, Jie Jin, Vidh Murthy, Masamitsu Yanada, Arnold Ganser
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Editorial Material
Hematology
Peter Hokland
Summary: This article explores how patients are handled within widely varying health systems, including both strained economies and more affluent ones, providing a global view.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Biographical-Item
Hematology
Peter Hokland
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Oncology
Signe Neldeborg, Johannes Frasez Soerensen, Charlotte Thornild Moller, Marie Bill, Zongliang Gao, Rasmus O. Bak, Kasper Holm, Boe Sorensen, Mette Nyegaard, Yonglun Luo, Peter Hokland, Magnus Stougaard, Maja Ludvigsen, Christian Kanstrup Holm
Summary: Oncogenic fusion drivers in hematological cancers can be targeted using a new dual intron-targeting CRISPR-Cas9 treatment strategy. This strategy can efficiently disrupt fusion genes without requiring precise knowledge of the breakpoints in t(8;21) AML. In vitro and in vivo experiments showed significant reduction in cell growth and tumor growth in response to disruption of RUNX1-RUNX1T1. These findings were confirmed in primary cells from an AML patient.
Article
Hematology
Soren Thorgaard Bonlokke, Christian Fenger-Eriksen, Hans Beier Ommen, Anne-Mette Hvas
Summary: This study investigated the dynamics of fibrinolysis in patients with hematological cancer and found that patients with lymphoma exhibited impaired fibrinolysis, while patients with acute promyelocytic leukemia and light-chain amyloidosis showed hyperfibrinolysis.