Article
Biochemistry & Molecular Biology
Ze-Wei Huang, Xue-Ning Zhang, Ling Zhang, Ling-Ling Liu, Jing-Wen Zhang, Yu-Xiang Sun, Jue-Qiong Xu, Quentin Liu, Zi-Jie Long
Summary: This article discusses the challenges of applying immunotherapy in acute myeloid leukemia (AML) and presents the STAT5-lactate-PD-L1 network, which may help identify which AML patients can benefit from PD-1/PD-L1-based immunotherapy.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2023)
Article
Oncology
Zihao Zhang, Yukai Lu, Yan Qi, Yang Xu, Song Wang, Fang Chen, Mingqiang Shen, Mo Chen, Naicheng Chen, Lijing Yang, Shilei Chen, Fengchao Wang, Yongping Su, Mengjia Hu, Junping Wang
Summary: CDK19 is involved in the regulation of HSC and AML cell proliferation via the p53-p21 pathway.
Article
Medicine, Research & Experimental
Lixiazi He, Christian Arnold, Judith Thoma, Christian Rohde, Maksim Kholmatov, Swati Garg, Cheng-Chih Hsiao, Linda Viol, Kaiqing Zhang, Rui Sun, Christina Schmidt, Maike Janssen, Tara MacRae, Karin Huber, Christian Thiede, Josee Hebert, Guy Sauvageau, Julia Spratte, Herbert Fluhr, Gabriela Aust, Carsten Muller-Tidow, Christof Niehrs, Gislene Pereira, Joerg Hamann, Motomu Tanaka, Judith B. Zaugg, Caroline Pabst
Summary: The study reveals that GPR56(+) LSC compartments are promoted in a complex network, and the regulation of the Wnt pathway can affect the quantity and gene expression of LSC subsets. CDK7 inhibitors can suppress both enriched LSC subsets in vivo, and combined with the Bcl-2 inhibitor venetoclax can have synergistic effects.
EMBO MOLECULAR MEDICINE
(2022)
Article
Cell Biology
Qi Zhu, Feng Liang, Shufang Cai, Xiaorong Luo, Tianqi Duo, Ziyun Liang, Zuyong He, Yaosheng Chen, Delin Mo
Summary: KDM4A deficiency in skeletal muscle impairs muscle formation and regeneration, and inhibits myogenic cell proliferation and differentiation.
CELL DEATH & DISEASE
(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.
Review
Biochemical Research Methods
Pedro Casado, Pedro R. Cutillas
Summary: Acute myeloid leukemia (AML) is a heterogeneous cancer with no cure, and current therapies have limited success due to disease complexity. Proteomics and phosphoproteomics studies provide insights into AML biology and potential biomarkers and drug targets. The use of these approaches can contribute to the development of precision medicine for AML patients.
MOLECULAR & CELLULAR PROTEOMICS
(2023)
Article
Medicine, Research & Experimental
Na Man, Gloria Mas, Daniel L. Karl, Jun Sun, Fan Liu, Qin Yang, Miguel Torres-Martin, Hidehiro Itonaga, Concepcion Martinez, Shi Chen, Ye Xu, Stephanie Duffort, Pierre-Jacques Hamard, Chuan Chen, Beth E. Zucconi, Luisa Cimmino, Feng-Chun Yang, Mingjiang Xu, Philip A. Cole, Maria E. Figueroa, Stephen D. Nimer
Summary: This study identified a tumor suppressor role of the acetyltransferase p300 in MDS, with loss of p300 enhancing HSPC proliferation and self-renewal, ultimately increasing leukemogenicity. Mechanistically, loss of p300 altered gene expression and promoted leukemia development, while activating p300 activity countered these effects. This suggests a potential therapeutic application of p300 activators in treating MDS with TET2 mutations.
Article
Oncology
Katherine Clesham, Vanessa Walf-Vorderwulbecke, Luca Gasparoli, Clemence Virely, Sandra Cantilena, Alexia Tsakaneli, Sarah Inglott, Stuart Adams, Sujith Samarasinghe, Jack Bartram, Gareth Williams, Jasper de Boer, Owen Williams
Summary: This study demonstrates that withaferin A (WFA), a steroidal lactone, can rapidly eliminate c-MYB protein, inhibit c-MYB target gene expression, reduce leukemia cell viability, decrease colony formation, and impair disease progression. The activity of WFA against AML depends on c-MYB modulation and can be partially reversed by a stabilized c-MYB mutant.
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)
Review
Oncology
Akihiko Yokoyama
Summary: The homeostasis of the hematopoietic system relies on hematopoietic stem cells (HSCs) at the top of the hierarchy, which possess the unique ability to self-renew. Mutated MLL proteins in leukemia activate a transcriptional system that promotes aberrant self-renewal of leukemia stem cells, overriding the programmed differentiation of non-HSC hematopoietic progenitors. Inhibitors targeting components of this transcriptional activation system are effective in reducing the leukemogenic potential.
Article
Oncology
Yukai Lu, Lijing Yang, Mingqiang Shen, Zihao Zhang, Song Wang, Fang Chen, Naicheng Chen, Yang Xu, Hao Zeng, Mo Chen, Shilei Chen, Fengchao Wang, Mengjia Hu, Junping Wang
Summary: This study reveals that Tespa1 is important for the maintenance of hematopoietic stem cells (HSCs) and leukemia stem cells (LSCs) and plays a crucial role in HSC and LSC self-renewal. Tespa1 prevents degradation of c-Myc protein in HSCs and is essential for AML cell growth. Tespa1 deficiency suppresses leukemogenesis and LSC maintenance.
Article
Multidisciplinary Sciences
Aysegul Erdem, Silvia Marin, Diego A. Pereira-Martins, Roldan Cortes, Alan Cunningham, Maurien G. Pruis, Bauke de Boer, Fiona A. J. van den Heuvel, Marjan Geugien, Albertus T. J. Wierenga, Annet Z. Brouwers-Vos, Eduardo M. Rego, Gerwin Huls, Marta Cascante, Jan Jacob Schuringa
Summary: This study uncovers the metabolic heterogeneity of acute myeloid leukemia (AML) and identifies Pyruvate dehydrogenase kinase 1 (PDK1) as a targetable determinant of different metabolic states in distinct subtypes of AML. This finding provides potential targets for the treatment of AML, a genetically heterogeneous disease.
NATURE COMMUNICATIONS
(2022)
Article
Medicine, Research & Experimental
Alhomidi Almotiri, Hamed Alzahrani, Juan Bautista Menendez-Gonzalez, Ali Abdelfattah, Badi Alotaibi, Lubaid Saleh, Adelle Greene, Mia Georgiou, Alex Gibbs, Amani Alsayari, Sarab Taha, Leigh-anne Thomas, Dhruv Shah, Sarah Edkins, Peter Giles, Marc P. Stemmler, Simone Brabletz, Thomas Brabletz, Ashleigh S. Boyd, Florian A. Siebzehnrubl, Neil P. Rodrigues
Summary: The study suggests that loss of Zeb1 in adult stem cells leads to significant defects in stem cell renewal and differentiation, which are associated with leukemia signaling. Therefore, Zeb1 plays a crucial role as a transcriptional regulator in hematopoiesis, coordinating HSC self-renewal and differentiation to suppress the potential development of AML.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Multidisciplinary Sciences
S. S. Hoepner, Ana Raykova, R. Radpour, M. A. Amrein, D. Koller, G. M. Baerlocher, C. Riether, A. F. Ochsenbein
Summary: The study demonstrates that LIGHT and its receptor LT beta R promote quiescence and self-renewal of HSCs, while LT beta R deficiency contributes to survival in a mouse leukemia model.
NATURE COMMUNICATIONS
(2021)
Article
Cell Biology
Vasiliki Symeonidou, Helene Jakobczyk, Salem Bashanfer, Camille Malouf, Foteini Fotopoulou, Rishi S. Kotecha, Richard A. Anderson, Andrew J. Finch, Katrin Ottersbach
Summary: This study reveals the unique biology of infant MLL-AF4-driven acute lymphoblastic leukemia, especially its prenatal origin, providing new insights and directions for the treatment of this disease.
Article
Cell Biology
Dagmara McGuinness, Suhaib Mohammed, Laura Monaghan, Paul A. Wilson, David B. Kingsmore, Oliver Shapter, Karen S. Stevenson, Shana M. Coley, Luke Devey, Robert B. Kirkpatrick, Paul G. Shiels
Article
Chemistry, Organic
Paul B. White, Sjoerd J. Rijpkema, Roderick P. Bunschoten, Jasmin Mecinovic
Review
Oncology
Laura Monaghan, Matthew E. Massett, Roderick P. Bunschoten, Alex Hoose, Petrisor-Alin Pirvan, Robert M. J. Liskamp, Heather G. Jorgensen, Xu Huang
FRONTIERS IN ONCOLOGY
(2019)
Meeting Abstract
Hematology
Laura Monaghan, Matthew Edward Massett, Roderick P. Bunschoten, Petrisor Alin Pirvan, Alex Hoose, Taeju Park, Joana Bittencourt-Silvestre, Robert M. J. Liskamp, Heather G. Jorgensen, Xu Huang
Review
Oncology
Shaun David Patterson, Mhairi Copland
Summary: Tyrosine kinase inhibitors (TKIs) are effective for treating chronic myeloid leukaemia (CML), but TKI-resistant leukemia stem cells (LSCs) prevent a complete cure. The bone marrow immune microenvironment (BME) plays a role in therapy resistance by providing protection to LSCs. This review discusses the interactions between CML cells and the immune microenvironment and explores potential therapeutic vulnerabilities.
CURRENT HEMATOLOGIC MALIGNANCY REPORTS
(2023)
Review
Biochemistry & Molecular Biology
Laura Monaghan, Dasa Longman, Javier F. Caceres
Summary: mRNA surveillance pathways play a crucial role in maintaining accurate gene expression and translation homeostasis. Studying these pathways can help us understand how cellular mRNA levels are regulated, how defective mRNAs are eliminated, and how dysregulation can contribute to human disease.