Article
Cell Biology
Xi Xu, Wenwen Zhang, Li Xuan, Yanhui Yu, Wen Zheng, Fang Tao, Jacqelyn Nemechek, Chong He, Weiwei Ma, Xue Han, Siyu Xie, Minyi Zhao, Jian Wang, Yuhua Qu, Qifa Liu, John M. Perry, Linjia Jiang, Meng Zhao
Summary: “T cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy. In this study, a rare inhibitory receptor called programmed cell death 1 (PD-1) was identified as a marker for leukemia stem cells (LSCs) in T-ALL. Blocking PD-1 significantly eradicated LSCs and suppressed disease progression, and combination therapy with PD-1 blockade and chemotherapy extended survival. Mechanistically, PD-1+ LSCs had high NOTCH1-MYC activity and were protected against apoptosis. These findings provide a therapeutic approach for eliminating LSCs in T-ALL.”
NATURE CELL BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Wencan Zhang, Xu Cao, Xiancai Zhong, Hongmin Wu, Yun Shi, Mingye Feng, Yi-Chang Wang, David Ann, Yousang Gwack, Yate-Ching Yuan, Weirong Shang, Zuoming Sun
Summary: The study finds that the nuclear receptor coactivator SRC2 enhances CD4+ T cell activation by recruiting c-Myc and upregulating amino acid transporter Slc7a5, thereby stimulating immune responses. Mice deficient in SRC2 in T cells are resistant to EAE but susceptible to C. rodentium. SRC2fl/fl/CD4Cre mice display impaired T cell proliferation, cytokine production, and differentiation in vitro and in vivo. Therefore, SRC2 is essential for CD4+ T cell activation and could be a potential drug target for controlling CD4+ T cell-mediated autoimmunity.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Multidisciplinary Sciences
Dhananjaya Pal, Kendra R. Vann, Shweta Joshi, Namood E. Sahar, Guillermo A. Morales, Dalia El-Gamal, Tatiana G. Kutateladze, Donald L. Durden
Summary: The study developed a first-in-class inhibitor SRX3262 that simultaneously blocks three driver pathways of MCL and overcomes resistance. The inhibitor destabilizes c-MYC, induces apoptosis, providing a new approach to treat MCL.
Article
Cell Biology
Xingming Zhang, Lou Geng, Li Yang, Yingying Wang, Zhihui Zou, Youping Zhang, Hanzhang Xu, Hu Lei, Yang Cao, Yingli Wu, Wenli Gu, Li Zhou
Summary: Despite progress in treating T-cell acute lymphoblastic leukemia (T-ALL), the prognosis for adult T-ALL remains poor. Anlotinib, an oral tyrosine kinase inhibitor used for lung cancer, has shown promise as an anti-T-ALL drug. Comprehensive in vitro and in vivo studies were conducted to investigate the mechanisms underlying anlotinib's effects on T-ALL.
CELLULAR SIGNALLING
(2023)
Article
Cell Biology
Eva-Maria Cox, Mohamed El-Behi, Stefanie Ries, Johannes F. Vogt, Vivien Kohlhaas, Thomas Michna, Benoit Manfroi, Mona Al-Maarri, Florian Wanke, Boaz Tirosh, Corinne Pondarre, Harry Lezeau, Nir Yogev, Romy Mittenzwei, Marc Descatoire, Sandra Weller, Jean-Claude Weill, Claude-Agnes Reynaud, Pierre Boudinot, Luc Jouneau, Stefan Tenzer, Ute Distler, Anne Rensing-Ehl, Christoph Koenig, Julian Staniek, Marta Rizzi, Aude Magerus, Frederic Rieux-Laucat, F. Thomas Wunderlich, Nadine Hoevelmeyer, Simon Fillatreau
Summary: This study reveals that AKT is involved in the formation of marginal zone (MZ) B cells in both mice and humans. By manipulating AKT signaling in B cells and its impact on FoxO transcription factors, the AKT-FoxO axis is identified as a switch for MZ B cell formation in mice. This developmental pathway is conserved in humans, where AKT-dependent splenic IgD+CD27+ B cells are proposed as the equivalent of MZ B cells.
Article
Cell Biology
I-Lun Hsin, Huang-Pin Shen, Hui-Yi Chang, Jiunn-Liang Ko, Po-Hui Wang
Summary: The study revealed a novel mechanism of the PI3K/mTOR dual inhibitor, PQR309, in lowering cell viability in endometrial cancer cells by disrupting the PI3K/Akt/mTOR/c-Myc/mtp53 positive feedback loop.
Review
Oncology
Xin Wan, Wei Guo, Zhumei Zhan, Ou Bai
Summary: This review focuses on the functions, substrates, and expression of FBW7 in malignant lymphoproliferative disorders. FBW7, as a key component of UPS proteins and a critical tumor suppressor, plays an important role in controlling protein degradation and the development of various cancers.
FRONTIERS IN ONCOLOGY
(2022)
Article
Chemistry, Medicinal
Pragya Kumari, Subhashis Ghosh, Sourav Acharya, Paromita Mitra, Souryadip Roy, Shilpendu Ghosh, Moumita Maji, Sandeep Singh, Arindam Mukherjee
Summary: This study reveals a new class of drugs targeting oral squamous cell carcinoma stem cells, which inhibit the growth and differentiation of cancer stem cells by suppressing the expression of stemness genes and inducing differentiation markers.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Chenming Ni, Wenyu Liu, Kailian Zheng, Shiwei Guo, Bin Song, Wei Jing, Gang Li, Bo Li, Canrong Ni, Keqing Shi, Gang Jin, Guanzhen Yu
Summary: The study discovered the presence of the MLL-AFF4 fusion gene in acute leukemia and investigated the role of AFF4 in pancreatic tumorigenesis. The results showed that overexpression of AFF4 promoted cell proliferation and cell cycle progression, while two nucleotide metabolism enzymes, HPRT1 and IMPDH2, were upregulated. The study also found that AFF4 was regulated by the PI3K/c-Myc axis and was positively correlated with c-Myc and HPRT1/IMPDH2 expression in clinical PDAC samples. These findings establish AFF4 as a potential biomarker and therapeutic target for PDAC.
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
(2023)
Article
Oncology
Wenjuan Ma, Yan Wan, Jianxiang Zhang, Jianan Yao, Yifei Wang, Jinchang Lu, Hong Liu, Xiaorui Huang, Xiuyan Zhang, Haixia Zhou, Yulong He, Depei Wu, Jianrong Wang, Yun Zhao
Summary: This study reveals that GAS2 promotes T-cell leukemogenesis through its interaction with CXCR4 to activate NOTCH1/c-MYC pathway. Loss of GAS2 has a mild effect on normal hematopoiesis.
MOLECULAR ONCOLOGY
(2022)
Letter
Oncology
Long Chen, Anqi Ren, Yuan Zhao, Hangyu Chen, Qifang Wu, Mengzhu Zheng, Zijian Zhang, Tongcun Zhang, Wu Zhong, Jian Lin, Haichuan Zhu
Summary: In this study, the researchers discovered that TET1, a key participant in DNA epigenetic control, is highly upregulated in T-cell acute lymphoblastic leukemia (T-ALL) and is negatively correlated with patient prognosis. Knockdown of TET1 suppressed T-ALL growth and progression, suggesting that TET1 inhibition might be an effective way to treat T-ALL. Additionally, the researchers found that auranofin, a gold-containing compound, is a potent TET1 inhibitor, which can reprogram gene expression and inhibit T-ALL growth.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2023)
Review
Immunology
Kristoffer H. Johansen, Dominic P. Golec, Julie H. Thomsen, Pamela L. Schwartzberg, Klaus Okkenhaug
Summary: PI3K signaling is crucial for T cell activation, differentiation, and trafficking, with PI3K delta being the dominant isoform in T cells. It regulates T cell functions by controlling adhesion receptors and their interaction with antigen-presenting cells. Understanding the role of PI3K delta in T cell migration and localization is important for potential impacts of PI3K delta inhibitors on T cell redistribution and function.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Cell Biology
Guoxi Zhang, Junrong Zou, Jinglin Shi, Biao Qian, Kaiyang Qiu, Quanliang Liu, Tianpeng Xie, Zhihua He, Hui Xu, Yunfeng Liao, Yuting Wu, Yanmin Li, Guancheng Xiao, Yuanhu Yuan, Rihai Xiao, Gengqing Wu, Xiaofeng Zou
Summary: UBA2 expression is higher in clear cell renal cell carcinoma compared to normal tissues, and is significantly related to tumor size, Fuhrman grade, and tumor stage. Knockdown of UBA2 inhibits ccRCC cell growth, promotes apoptosis, and decreases key enzyme abundance of the SUMO modification system. Targeting UBA2 may have therapeutic potential against ccRCC.
CELL DEATH & DISEASE
(2021)
Article
Medicine, Research & Experimental
Zhuonan Liu, Tianshui Sun, Chiyuan Piao, Zhe Zhang, Chuize Kong
Summary: The study found that METTL13 is downregulated in ccRCC and is associated with poor prognosis; METTL13 can inhibit the growth and metastasis of ccRCC cells through multiple molecular mechanisms.
JOURNAL OF TRANSLATIONAL MEDICINE
(2021)
Article
Oncology
Yanchun Ma, Vera Bauer, Tanja Riedel, Fatima Ahmetlic, Nadine Homberg, Thomas P. Hofer, Martin Rocken, Ralph Mocikat
Summary: The study reveals that IL-10 suppresses ongoing immune responses in lymphoma and may be a potential target for immunotherapy.
Article
Cell Biology
Evisa Gjini, Chang-Bin Jing, Ashley T. Nguyen, Deepak Reyon, Emma Gans, Michiel Kesarsing, Joshua Peterson, Olga Pozdnyakova, Scott J. Rodig, Marc R. Mansour, Keith Joung, A. Thomas Look
DISEASE MODELS & MECHANISMS
(2019)
Article
Oncology
Elena Armenteros-Monterroso, Lu Zhao, Luca Gasparoli, Tony Brooks, Kerra Pearce, Marc R. Mansour, Joost H. A. Martens, Jasper de Boer, Owen Williams
Article
Hematology
Richard Burt, Aditi Dey, Sarah Aref, Melanie Aguiar, Ayse Akarca, Katharine Bailey, William Day, Steven Hooper, Amy Kirkwood, Kristina Kirschner, Soo-Wah Lee, Cristina Lo Celso, Jiten Manji, Marc R. Mansour, Teresa Marafioti, Rachel J. Mitchell, Robert C. Muirhead, Kenton Cheuk Yan Ng, Constandina Pospori, Ignazio Puccio, Krisztina Zuborne-Alapi, Erik Sahai, Adele K. Fielding
Review
Cell Biology
Sunniyat Rahman, Marc R. Mansour
DISEASE MODELS & MECHANISMS
(2019)
Letter
Hematology
Catherine Hockings, Satyen Gohil, Robin Dowse, Yvette Hoade, Marc R. Mansour, Rosemary E. Gale, David C. Linch, Anupama Rao, Elspeth M. Payne
BRITISH JOURNAL OF HAEMATOLOGY
(2020)
Article
Oncology
Theresa E. Leon, Tanya Rapoz-D'Silva, Cosetta Bertoli, Sunniyat Rahman, Michael Magnussen, Brian Philip, Nadine Farah, Simon E. Richardson, Sara Ahrabi, Jose Afonso Guerra-Assuncao, Rajeev Gupta, Elisabeth P. Nacheva, Stephen Henderson, Javier Herrero, David C. Linch, Robertus A. M. de Bruin, Marc R. Mansour
Letter
Hematology
Andrew J. Wilson, Ethan Troy-Barnes, Maryam Subhan, Fiona Clark, Rajeev Gupta, Adele K. Fielding, Panagiotis Kottaridis, Marc R. Mansour, Jenny O'Nions, Elspeth Payne, Naina Chavda, Robert Baker, Kirsty Thomson, Asim Khwaja
BRITISH JOURNAL OF HAEMATOLOGY
(2020)
Letter
Hematology
Sarah Leong, Sarah Inglott, Foteini Papaleonidopoulou, Karen Orfinada, Philip Ancliff, Jack Bartram, Ben Carpenter, Adele K. Fielding, Sara Ghorashian, Victoria Grandage, Rajeev Gupta, Rachael Hough, Asim Khwaja, Vesna Pavasovic, Anupama Rao, Sujith Samarasinghe, Ajay Vora, Marc R. Mansour, David O'Connor
Letter
Oncology
Thomas A. Fox, Ben Carpenter, Mary Taj, Martha Perisoglou, Emma Nicholson, Anna Castleton, Johnathon Elliot, Ben Uttenthal, Callum Wright, Richard Halsey, Asim Khwaja, Victoria Grandage, Marc R. Mansour, Adele K. Fielding, Rachael Hough
LEUKEMIA & LYMPHOMA
(2021)
Review
Hematology
Rachael Pocock, Nadine Farah, Simon E. Richardson, Marc R. Mansour
Summary: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy of T-cell progenitors that remains challenging to treat despite improvements in survival outcomes over the past 50 years. Relapsed and refractory cases are particularly difficult to manage, and T-ALL is proving to be a more challenging immunotherapeutic target compared to B-ALL. Understanding the basic biology of T-ALL is crucial in repurposing established treatments and developing novel therapeutic approaches.
BRITISH JOURNAL OF HAEMATOLOGY
(2021)
Letter
Oncology
Mary M. Taj, Anthony V. Moorman, Lina Hamadeh, Arnaud Petit, Vahid Asnafi, Fanny Alby-Laurent, Ajay Vora, Marc R. Mansour, Rosemary Gale, Sylvie Chevret, John Moppett, Andre Baruchel, Elizabeth Macintyre
Article
Biochemistry & Molecular Biology
Shuning He, Mark W. Zimmerman, Hillary M. Layden, Alla Berezovskaya, Julia Etchin, Megan W. Martel, Grace Thurston, Chang-Bin Jing, Ellen van Rooijen, Charles K. Kaufman, Scott J. Rodig, Leonard I. Zon, E. Elizabeth Patton, Marc R. Mansour, A. Thomas Look
Summary: Loss of the NF1 tumor suppressor gene can lead to aggressive melanomas with a high risk of treatment failure. This study established a zebrafish model of NF1-mutant melanomas harboring PTEN loss and demonstrated that mTOR inhibitors and a three-drug combination can potently induce apoptosis in NF1/PTEN-deficient melanoma cells, supporting the need for early-stage clinical trials in patients.
Review
Medicine, General & Internal
Victor Llombart, Marc R. Mansour
Summary: c-MYC plays a crucial role in regulating gene expression and is involved in tumor initiation and maintenance. Inhibition of MYC shows promising anti-proliferative effects and tumor regression, making it a potential therapeutic target for cancer treatment.
Article
Hematology
Paul M. Maciocia, Patrycja A. Wawrzyniecka, Nicola C. Maciocia, Amy Burley, Thaneswari Karpanasamy, Sam Devereaux, Malika Hoekx, David O'Connor, Theresa Leon, Tanya Rapoz-D'Silva, Rachael Pocock, Sunniyat Rahman, Giuseppe Gritti, Diana C. Yanez, Susan Ross, Tessa Crompton, Owen Williams, Lydia Lee, Martin A. Pule, Marc R. Mansour
Summary: CCR9 expression is found in the majority of T-ALL cases, making it a potential target for CAR-T cell therapy. CAR-T cells targeting CCR9 can effectively inhibit leukemia cell proliferation without harming healthy T cells, providing a promising treatment strategy for T-ALL.
Article
Oncology
Juliette Roels, Morgan Thenoz, Mattias Landfors, Stien De Coninck, Lisa Demoen, Lien Provez, Anna Kuchmiy, Steven Strubbe, Lindy Reunes, Tim Pieters, Filip Matthijssens, Wouter Van Loocke, Busra Erarslan-Uysal, Paulina Richter-Pechanska, Ken Declerck, Tim Lammens, Barbara De Moerloose, Dieter Deforce, Filip Van Nieuwerburgh, Laurence C. Cheung, Rishi S. Kotecha, Marc R. Mansour, Bart Ghesquiere, Guy Van Camp, Wim Vanden Berghe, Jerzy R. Kowalczyk, Tomasz Szczepanski, Utpal P. Dave, Andreas E. Kulozik, Steven Goossens, David J. Curtis, Tom Taghon, Malgorzata Dawidowska, Sofie Degerman, Pieter Van Vlierberghe
BLOOD CANCER DISCOVERY
(2020)