Article
Medicine, Research & Experimental
Filip Matthijssens, Nitesh D. Sharma, Monique Nysus, Christian K. Nickl, Huining Kang, Dominique R. Perez, Beatrice Lintermans, Wouter Van Loocke, Juliette Roels, Sofie Peirs, Lisa Demoen, Tim Pieters, Lindy Reunes, Tim Lammens, Barbara De Moerloose, Filip Van Nieuwerburgh, Dieter L. Deforce, Laurence C. Cheung, Rishi S. Kotecha, Martijn D. P. Risseeuw, Serge Van Calenbergh, Takeshi Takarada, Yukio Yoneda, Frederik W. van Delft, Richard B. Lock, Seth D. Merkley, Alexandre Chigaev, Larry A. Sklar, Charles G. Mullighan, Mignon L. Loh, Stuart S. Winter, Stephen P. Hunger, Steven Goossens, Eliseo F. Castillo, Wojciech Ornatowski, Pieter Van Vlierberghe, Ksenia Matlawska-Wasowska
Summary: The study demonstrates that the upregulation of RUNX2 acts as a dependency factor in high-risk subtypes of human T-ALL by regulating tumor metabolism and leukemic cell migration simultaneously.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Review
Oncology
Ziting Zhang, Kun Yang, Han Zhang
Summary: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive and heterogeneous subtype of cancer. Recent studies have shown the important roles of leukemia-initiating cells (LICs) and leukemic niches in the initiation and progression of T-ALL, leading to the development of targeted therapies.
Article
Biochemistry & Molecular Biology
Xiaosi Hu, Hongtao Pan, Shuai Zhou, Qing Pang, Yong Wang, Chao Zhu, Huichun Liu, Hao Jin, Aman Xu
Summary: This study investigated the role and potential mechanism of HS1-binding protein 3 (HS1BP3) in hepatocellular carcinoma (HCC). The results showed that high expression of HS1BP3 was significantly associated with poor prognosis in HCC. Silence of HS1BP3 inhibited proliferation and migration, and promoted apoptosis in HCC cells. Moreover, estrogen receptor 1 (ESR1) suppressed HCC proliferation by fusion with HS1BP3 promoter.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Medicine, Research & Experimental
Xueliang Gao, Shenghui Qin, Yongxia Wu, Chen Chu, Baishan Jiang, Roger H. Johnson, Dong Kuang, Jie Zhang, Xi Wang, Anand Mehta, Kenneth D. Tew, Gustavo W. Leone, Xue-Zhong Yu, Haizhen Wang
Summary: PFKP, the major isoform of PFK1 in T-ALL, functions as a nucleocytoplasmic shuttling protein with nuclear export and localization sequences. Nuclear PFKP promotes the expression of CXCR4 to facilitate T-ALL cell invasion, which can be blocked with CXCR4 antagonists. The presence of nuclear PFKP in T cell malignancy correlates with poor survival and suggests its potential as a diagnostic marker.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Review
Oncology
Francesco Tamiro, Andrew P. Weng, Vincenzo Giambra
Summary: Leukemia-initiating cells (LIC) are unique cells in different types of leukemia that have self-renewing capabilities and produce tumors, which are functionally distinct from bulk leukemia cells. Current conventional treatments are not effective in eliminating LICs, hence innovative therapeutics targeting LICs hold promise for developing an effective cure for ALL.
Article
Oncology
Qiaoling Xiao, Li Lei, Jun Ren, Meixi Peng, Yipei Jing, Xueke Jiang, Junpeng Huang, Yonghong Tao, Can Lin, Jing Yang, Minghui Sun, Lisha Tang, Xingyu Wei, Zailin Yang, Ling Zhang
Summary: This study found decreased levels of m(6)A RNA modification in acute myeloid leukemia (AML) with nucleophosmin 1 (NPM1) mutations. The high expression of fat mass and obesity-associated protein (FTO) was responsible for the suppression of m(6)A modification. FTO upregulation facilitated leukemic cell survival through activating the PDGFRB/ERK signaling axis.
FRONTIERS IN ONCOLOGY
(2022)
Article
Immunology
Kunlong Zhang, Jun Lu, Fang Fang, Yongping Zhang, Juanjuan Yu, Yanfang Tao, Wenyuan Liu, Lihui Lu, Zimu Zhang, Xinran Chu, Jianwei Wang, Xiaolu Li, Yuanyuan Tian, Zhiheng Li, Qian Li, Xu Sang, Li Ma, Ningling Wang, Jian Pan, Shaoyan Hu
Summary: FYB1 gene plays an important role in regulating self-renewal of T-ALL cells by activating IGLL1, suggesting a promising therapeutic target for T-ALL patients.
JOURNAL OF IMMUNOLOGY RESEARCH
(2023)
Article
Chemistry, Multidisciplinary
Ruinan Jia, Tao Sun, Xin Zhao, Guosheng Li, Yuan Xia, Ying Zhou, Wei Li, Daoxin Ma, Jingjing Ye, Min Ji, Chunyan Ji
Summary: It is observed that adipocytes in the bone marrow microenvironment (BMM) of T-ALL patients increase significantly after exposure to chemotherapeutic drugs. Adipocytes attract T-ALL cells through releasing CXCL13 and support leukemia cell survival by activating the Notch1 signaling pathway. In addition, the differentiation of BMSCs to adipocytes induced by DEX contributes to MRD in T-ALL and can be targeted for reducing the recurrence rate.
Article
Hematology
Cedric S. Tremblay, Jesslyn Saw, Jacqueline A. Boyle, Katharina Haigh, Veronique Litalien, Hannah McCalmont, Kathryn Evans, Richard B. Lock, Stephen M. Jane, Jody J. Haigh, David J. Curtis
Summary: Interleukin-7 (IL-7) is important for the growth and resistance to chemotherapy of T-cell acute lymphoblastic leukemia (T-ALL), especially the early T-cell precursor subtype (ETP-ALL). Signal transducer and activator of transcription (STAT5) is universally activated in ETP-ALL and plays a crucial role in its development. Inhibition of STAT5 is necessary to block the supportive signals provided by IL-7 and eradicate leukemia stem cells (LSCs).
Article
Multidisciplinary Sciences
David M. Schauder, Jian Shen, Yao Chen, Moujtaba Y. Kasmani, Matthew R. Kudek, Robert Burns, Weiguo Cui
Summary: During acute viral infections, CD8 T cells encounter various antigenic and inflammatory signals, leading to differentiation into memory cells or death. Research has shown that memory precursor effector cells maintain open enhancers for key memory genes, with a high enrichment of E2A binding sites. E2A directly regulates the accessibility of enhancers for memory-related genes, increasing the frequency of memory precursor effector cells and accelerating memory cell formation while reducing short-lived effector cells.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Medicine, General & Internal
Robert Chiesa, Christos Georgiadis, Farhatullah Syed, Hong Zhan, Annie Etuk, Soragia Athina Gkazi, Roland Preece, Giorgio Ottaviano, Toni Braybrook, Jan Chu, Agnieszka Kubat, Stuart Adams, Rebecca Thomas, Kimberly Gilmour, David O'Connor, Ajay Vora, Waseem Qasim
Summary: Base editing technique has been used to inactivate genes and treat relapsed childhood T-cell leukemia with promising results.
NEW ENGLAND JOURNAL OF MEDICINE
(2023)
Article
Cell Biology
Jingjing Ma, Zhixian He, Hongwei Zhang, Wensheng Zhang, Sheng Gao, Xiaojian Ni
Summary: The study showed that SEC61G is highly expressed in breast cancer and predicts poor prognosis. Its overexpression promotes breast cancer cell proliferation and migration by modulating glycolysis. SEC61G is transcriptionally regulated by E2F1 and may serve as a promising therapeutic target in breast cancer treatment.
CELL DEATH & DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Ningfei An, Saira Khan, Molly K. K. Imgruet, Lia Jueng, Sandeep Gurbuxani, Megan E. E. McNerney
Summary: -7/del(7q) is commonly found in myeloid neoplasms. CUX1, located on 7q22, is a transcription factor associated with poor prognosis when mutated. CUX1 deficiency and oncogenic RAS mutations are found to be linked and promote leukemogenesis. This research indicates a potential therapy for malignancies with CUX1 inactivation.
Article
Cell Biology
Ling Zhang, Jieying Wu, Yashu Feng, Bijay Khadka, Zhigang Fang, Jiaming Gu, Baoqiang Tang, Ruozhi Xiao, Guangjin Pan, Jia-Jun Liu
Summary: Leukemia-initiating cells in T-ALL patients exhibit overexpression of beta-catenin, leading to therapy resistance and subsequent shift in dependency towards Notch signaling pathway. These two pathways mutually compensate each other to maintain stem cell phenotype in T-ALL.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Medicine, General & Internal
Delia Codruta Popa, Andreea Serbanica, Radu Obrisca, Ionut Serbanica, Letitia Radu, Cristina Jercan, Andra Marcu, Ana Bica, Minodora Asan, Madalina Petran, Mihaela Dragomir, Cerasela Jardan, Valeria Tica, Anca Gheorghe, Irina Stoian, Daniel Coriu, Anca Colita, Andrei Colita
Summary: Acute lymphoblastic leukemia (ALL) is the most common cancer in children, with treatment outcomes and survival rates varying depending on the type of ALL. Advances in flow cytometry immunophenotyping and PCR amplification of antigen-receptor genes have improved patient management and survival rates for ALL, but clinical challenges persist.
FRONTIERS IN MEDICINE
(2022)
Article
Hematology
Annatina S. Schnegg-Kaufmann, Julie A. I. Thoms, Golam Sarower Bhuyan, Henry R. Hampton, Lachlin Vaughan, Kayleigh Rutherford, Purvi M. Kakadia, Hui Mei Lee, Emma M. V. Johansson, Timothy W. Failes, Greg M. Arndt, Jason Koval, Robert Lindeman, Pauline Warburton, Alba Rodriguez-Meira, Adam J. Mead, Ashwin Unnikrishnan, Sarah Davidson, Mark N. Polizzotto, Mark Hertzberg, Elli Papaemmanuil, Stefan K. Bohlander, Omid R. Faridani, Christopher J. Jolly, Fabio Zanini, John E. Pimanda
Summary: Myelodysplastic neoplasms (MDSs) and chronic myelomonocytic leukemia (CMML) are clonal disorders driven by acquired somatic mutations. Hypomethylating agents (HMAs) can modify the clinical course of these diseases. Clinical improvement may be related to improved differentiation capacity of mutated hematopoietic stem cells.
Article
Oncology
Laurence C. Cheung, Carlos Aya-Bonilla, Mark N. Cruickshank, Sung K. Chiu, Vincent Kuek, Denise Anderson, Grace-Alyssa Chua, Sajla Singh, Joyce Oommen, Emanuela Ferrari, Anastasia M. Hughes, Jette Ford, Elena Kunold, Maria C. Hesselman, Frederik Post, Kelly E. Faulk, Erin H. Breese, Erin M. Guest, Patrick A. Brown, Mignon L. Loh, Richard B. Lock, Ursula R. Kees, Rozbeh Jafari, Sebastien Malinge, Rishi S. Kotecha
Summary: In infants with KMT2A-rearranged B-cell acute lymphoblastic leukemia (ALL), hypomethylating agents combined with most conventional chemotherapeutic agents showed additive effects in vitro, but antagonistic effects were observed in a subset of samples. Single agent treatment with azacitidine and decitabine significantly prolonged in vivo survival in KMT2A-rearranged infant ALL xenografts. Differential genome-wide DNA methylation, changes in gene expression, and thermal proteome profiling were observed in KMT2A-rearranged infant ALL cell lines treated with azacitidine and decitabine. The selective BCL-2 inhibitor, venetoclax, exhibited in vitro additivity when combined with hypomethylating or conventional chemotherapeutic agents. Addition of venetoclax to azacitidine resulted in a significant in vivo survival advantage, indicating the therapeutic potential of this combination in improving outcomes for infants with KMT2A-rearranged ALL.
Article
Hematology
Cedric S. Tremblay, Jesslyn Saw, Jacqueline A. Boyle, Katharina Haigh, Veronique Litalien, Hannah McCalmont, Kathryn Evans, Richard B. Lock, Stephen M. Jane, Jody J. Haigh, David J. Curtis
Summary: Interleukin-7 (IL-7) is important for the growth and resistance to chemotherapy of T-cell acute lymphoblastic leukemia (T-ALL), especially the early T-cell precursor subtype (ETP-ALL). Signal transducer and activator of transcription (STAT5) is universally activated in ETP-ALL and plays a crucial role in its development. Inhibition of STAT5 is necessary to block the supportive signals provided by IL-7 and eradicate leukemia stem cells (LSCs).
Article
Oncology
Joanna Randall, Kathryn Evans, Ben Watts, Christopher M. M. Smith, Keira Hughes, Eric J. J. Earley, Stephen W. W. Erickson, Jonathan A. A. Pachter, Beverly A. A. Teicher, Malcolm A. A. Smith, Richard B. B. Lock
Summary: Acute lymphoblastic leukemia (ALL) is a common cause of cancer-related mortality in children. The PI3K pathway has been associated with ALL, and duvelisib has shown efficacy as a dual inhibitor of PI3K delta and PI3K gamma. In this study, duvelisib demonstrated limited in vivo activity against pediatric ALL patient-derived xenografts (PDXs).
PEDIATRIC BLOOD & CANCER
(2023)
Article
Oncology
Keira Hughes, Kathryn Evans, Eric J. Earley, Christopher M. Smith, Stephen W. Erickson, Tim Stearns, Vivek M. Philip, Steven B. Neuhauser, Jeffrey H. Chuang, Emily L. Jocoy, Carol J. Bult, Beverly A. Teicher, Malcolm A. Smith, Richard B. Lock
Summary: Although the majority of children with acute lymphoblastic leukemia (ALL) can be cured, certain high-risk subtypes of pediatric ALL have poor treatment outcomes. This study investigated the in vivo efficacy of TAK-659 in patient-derived xenografts (PDXs) of pediatric ALL. The results showed that TAK-659 prolonged the time to event in six out of eight PDXs tested, but only one PDX achieved an objective response.
PEDIATRIC BLOOD & CANCER
(2023)
Article
Multidisciplinary Sciences
Jianwei Lin, Yiping Wu, Gaofei Tian, Daqi Yu, Eunjeong Yang, Wai Hei Lam, Zheng Liu, Yihang Jing, Shangyu Dang, Xiucong Bao, Jason Wing Hon Wong, Yuanliang Zhai, Xiang David Li
Summary: H3K79me2 is an important epigenetic mark involved in gene regulation, cellular differentiation, and disease progression. A nucleosome-based photoaffinity probe was used to identify menin as a reader of H3K79me2 in a nucleosomal context. Cryo-electron microscopy showed that menin interacts with the nucleosome through specific domains and recognizes the methylation mark through a p-cation interaction. In cells, menin is selectively associated with H3K79me2 on chromatin, particularly in gene bodies.
Article
Biochemistry & Molecular Biology
Zacary P. Germon, Jonathan R. Sillar, Abdul Mannan, Ryan J. Duchatel, Dilana Staudt, Heather C. Murray, Izac J. Findlay, Evangeline R. Jackson, Holly P. McEwen, Alicia M. Douglas, Tabitha McLachlan, John E. Schjenken, David A. Skerrett-Byrne, Honggang Huang, Marcella N. Melo-Braga, Maximilian W. Plank, Frank Alvaro, Janis Chamberlain, Geoff De Iuliis, R. John Aitken, Brett Nixon, Andrew H. Wei, Anoop K. Enjeti, Yizhou Huang, Richard B. Lock, Martin R. Larsen, Heather Lee, Vijesh Vaghjiani, Jason E. Cain, Charles E. de Bock, Nicole M. Verrills, Matthew D. Dun
Summary: Mutations in FLT3 gene are common in AML patients and associated with poor prognosis. This study found that oxidative stress affects growth and proliferation signaling pathways in FLT3 mutant AML. Inhibition of NOX2, an ROS-producing complex, increased apoptosis of FLT3-mutant AML cells. In mouse models, NOX2 inhibition reduced circulating cancer cells and combined treatment with NOX2 and FLT3 inhibitors improved survival.
Article
Cell Biology
Ernest Moles, Christopher B. Howard, Pie Huda, Mawar Karsa, Hannah McCalmont, Kathleen Kimpton, Alastair Duly, Yongjuan Chen, Yizhou Huang, Melinda L. Tursky, David Ma, Sonia Bustamante, Russell Pickford, Patrick Connerty, Sofia Omari, Christopher J. Jolly, Swapna Joshi, Sylvie Shen, John E. Pimanda, Alla Dolnikov, Laurence C. Cheung, Rishi S. Kotecha, Murray D. Norris, Michelle Haber, Charles E. de Bock, Klaartje Somers, Richard B. Lock, Kristofer J. Thurecht, Maria Kavallaris
Summary: High-risk childhood leukemia has a poor prognosis due to treatment failure and toxic side effects. Encapsulation of drugs in liposomal nanocarriers improves biodistribution and tolerability, but lacks selectivity for cancer cells. In this study, bispecific antibodies were generated to target PEGylated liposomal drugs to leukemic cells. These antibodies improved targeting and cytotoxic activity, with minimal harm to normal cells. Targeted delivery using bispecific antibodies enhanced leukemia suppression and extended overall survival, representing a promising platform for improved treatment of high-risk leukemia.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Cell Biology
Patrick Connerty, Richard B. Lock
Summary: Long noncoding RNAs (lncRNAs), defined as RNA transcripts longer than 200 nucleotides with no protein coding potential, have been found to be dysregulated in various cancers, including acute myeloid leukemia (AML). As survival rates for AML have plateaued, the identification of lncRNAs as novel biomarkers and therapeutic targets for AML is crucial. This review assesses key studies that have identified lncRNAs in AML and summarizes the current knowledge of their roles, including driving proliferation, differentiation block, therapy resistance, tumor suppression, and utility as biomarkers.
WILEY INTERDISCIPLINARY REVIEWS-RNA
(2023)
Article
Multidisciplinary Sciences
Ian C. H. Lee, Sergey Tumanov, Jason W. H. Wong, Roland Stocker, Joshua W. K. Ho
Summary: Mass spectrometry-based untargeted metabolomic and lipidomic approaches are widely used in biomedical research. A sample extraction method called Multi-ABLE has been developed for concurrent generation of proteomic, metabolomic, and lipidomic data. However, there is a lack of a unified bioinformatics pipeline for processing and analysis of these data. A new R pipeline called MultiABLER is presented here as a unified and simple upstream processing and analysis pipeline for metabolomics and lipidomics datasets.
Article
Health Care Sciences & Services
Aya El Helali, Tai-Chung Lam, Elaine Yee-Ling Ko, David J. H. Shih, Chun Kau Chan, Charlene H. L. Wong, Jason W. H. Wong, Lydia W. T. Cheung, Johnny K. S. Lau, Anthony P. Y. Liu, Ann S. Y. Chan, Herbert H. Loong, Stephen Tak Sum Lam, Godfrey Chi-Fung Chan, Victor H. F. Lee, Kwok Keung Yuen, Wai-Tong Ng, Anne W. M. Lee, Edmond S. K. Ma
Summary: This study investigated the feasibility of the HKU-HKSH Multi-disciplinary Molecular Tumour Board (MTB) in determining genome-guided therapy for treatment-refractory solid cancers in Hong Kong. The results showed that MTB-guided treatment positively impacted patients' overall survival, illustrating the applicability of next-generation sequencing comprehensive gene profiling (CGP) in real-world clinical practice.
LANCET REGIONAL HEALTH-WESTERN PACIFIC
(2023)
Article
Oncology
Chelsea Mayoh, Jie Mao, Jinhan Xie, Gabor Tax, Shu-Oi Chow, Roxanne Cadiz, Karina Pazaky, Paulette Barahona, Pamela Ajuyah, Peter Trebilcock, Angela Malquori, Kate Gunther, Anica Avila, Doo Young Yun, Stephanie Alfred, Anjana Gopalakrishnan, Alvin Kamili, Marie Wong, Mark J. Cowley, Sophie Jessop, Loretta M. S. Lau, Toby N. Trahair, David S. Ziegler, Jamie I. Fletcher, Andrew J. Gifford, Maria Tsoli, Glenn M. Marshall, Michelle Haber, Vanessa Tyrrell, Timothy W. Failes, Greg M. Arndt, Richard B. Lock, Paul G. Ekert, M. Emmy M. Dolman
Summary: One-third of pediatric cancer patients enrolled in precision medicine programs do not receive therapeutic recommendations from molecular profiling. In order to find potential strategies for treating high-risk pediatric patients, a study conducted in vitro screening of 125 patient-derived samples against a library of 126 anticancer drugs. The results showed that high-throughput drug screening (HTS) can identify effective biomarker-driven therapeutic strategies for high-risk pediatric cancers.
Article
Oncology
Kinjal Shah, Ahmad Nasimian, Mehreen Ahmed, Lina Al Ashiri, Linn Denison, Wondossen Sime, Katerina Bendak, Iryna Kolosenko, Valentina Siino, Fredrik Levander, Caroline Palm-Apergi, Ramin Massoumi, Richard B. Lock, Julhash U. Kazi
Summary: Deregulation of BCL2 family proteins is critical in leukemia development, and inhibiting these proteins has become a common treatment for the disease. However, resistance to this treatment has compromised its effectiveness. In this study, a drug sensitivity prediction model was developed to assess the sensitivity of T-cell acute lymphoblastic leukemia (T-ALL) patients to the drug venetoclax. The results showed that PLK1 is a cooperating partner for the BCL2-mediated antiapoptotic program, and concurrent treatment using venetoclax and PLK1 inhibitors demonstrated a greater therapeutic effect on T-ALL.
BLOOD CANCER JOURNAL
(2023)
Article
Oncology
Hu Fang, Johanna Bertl, Xiaoqiang Zhu, Tai Chung Lam, Song Wu, David J. H. Shih, Jason W. H. Wong
Summary: Tumour mutational burden (TMB) is a predictive marker for immune checkpoint inhibitor (ICI) responsiveness, but its calculation using different genomic regions is unclear. This study found that cancer gene-based panels usually overestimate TMB compared to whole exome, potentially leading to misclassification of patients for ICI treatment. A statistical model was developed to unify TMB calculations and improve patient stratification for ICI treatment.
JOURNAL OF THE NATIONAL CANCER CENTER
(2023)
Article
Materials Science, Multidisciplinary
H. T. Kim Duong, Ashkan Abdibastami, Lucy Gloag, Andre Bongers, Saeed Shanehsazzadeh, Melanie Nelson, Aidan Cousins, Narges Bayat, Hannah Mccalmont, Richard B. Lock, Scott Sulway, Joanna Biazick, J. Justin Gooding, Richard D. Tilley
Summary: Magnetic particle imaging (MPI) has gained attention in biomedical imaging research due to its excellent signal intensity. This study demonstrated zinc doped iron oxide nanoparticles as excellent tracers for MPI, with significant enhancement in saturation magnetisation and MPI signal intensity compared to traditional iron oxide nanoparticles.
JOURNAL OF MAGNETISM AND MAGNETIC MATERIALS
(2023)