Article
Medicine, General & Internal
Courtney D. Dinardo, Harry P. Erba, Sylvie D. Freeman, Andrew H. Wei
Summary: Progress in acute myeloid leukaemia treatment has seen significant improvements in scientific understanding, prognostication tools, risk assessments, and incorporation of measurable residual disease into risk assessments. Recent updates in classification and recommendations by organizations such as WHO, ICC, and European LeukemiaNet have provided enhanced guidance for prognostic stratification and treatment response assessment. There have also been advancements in treatment options, leading to improved outcomes for both newly diagnosed and relapsed patients.
Article
Oncology
Simona Caruso, Biagio De Angelis, Francesca Del Bufalo, Roselia Ciccone, Samantha Donsante, Gabriele Volpe, Simona Manni, Marika Guercio, Michele Pezzella, Laura Iaffaldano, Domenico Alessandro Silvestris, Matilde Sinibaldi, Stefano Di Cecca, Angela Pitisci, Enrico Velardi, Pietro Merli, Mattia Algeri, Mariachiara Lodi, Valeria Paganelli, Marta Serafini, Mara Riminucci, Franco Locatelli, Concetta Quintarelli
Summary: The study demonstrates the potential of using off-the-shelf CAR.CD123-NK cells as a therapeutic strategy for paediatric AML patients, showing significant anti-leukaemia activity and improved safety compared to CAR.CD123-T cells.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2022)
Review
Oncology
Matthew R. Lordo, Steven D. Scoville, Akul Goel, Jianhua Yu, Aharon G. Freud, Michael A. Caligiuri, Bethany L. Mundy-Bosse
Summary: AML is an aggressive form of blood cancer with poor survival rates. Patients with AML often have defects in their immune system, particularly in NK cells. Recent studies are shedding light on the role of other ILC family members in AML, enhancing our understanding of AML treatment.
Review
Hematology
Sofiane Fodil, Marine Arnaud, Camille Vaganay, Alexandre Puissant, Etienne Lengline, Nuala Mooney, Raphael Itzykson, Lara Zafrani
Summary: The vascular microenvironment plays a crucial role in AML, with ECs and leukemic cells interacting to influence disease progression and complications.
Article
Oncology
Victoria Stavrou, Livingstone Fultang, Sarah Booth, Daniele De Simone, Arekdiusz Bartnik, Ugo Scarpa, Luciana Gneo, Silvia Panetti, Sandeep Potluri, Meaad Almowaled, Jonathan Barlow, Andris Jankevics, Gavin Lloyd, Andrew Southam, David A. Priestman, Paul Cheng, Warwick Dunn, Frances Platt, Hitoshi Endou, Charles Craddock, Karen Keeshan, Francis Mussai, Carmela De Santo
Summary: Acute myeloid leukaemia (AML) creates an immunosuppressive environment through induced arginine depletion. Serum amyloid A (SAA) in AML upregulates ARG2 expression, promotes cell viability, and activates iNKT cells, resulting in AML cell death. Therefore, stimulating iNKT cell activity has potential as an immunotherapy for AML.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2023)
Article
Hematology
Lucia Silla, Vanessa Valim, Annelise Pezzi, Maria da Silva, Ianae Wilke, Juliana Nobrega, Alini Vargas, Bruna Amorin, Bruna Correa, Bruna Zambonato, Fernanda Scherer, Joice Merzoni, Leo Sekine, Helen Huls, Laurence J. Cooper, Alessandra Paz, Dean A. Lee
Summary: In this study, repeated infusions of expanded NK cells showed promising outcomes in high-risk patients with relapsed or refractory AML, with high overall response and complete response rates. No dose-limiting toxicities or infusion-related complications were observed, indicating the safety and feasibility of this treatment approach.
BRITISH JOURNAL OF HAEMATOLOGY
(2021)
Article
Hematology
Xiaoling Xie, Wuju Zhang, Xuan Zhou, Zhixin Ye, Hao Wang, Yingqi Qiu, Yating Pan, Yuxing Hu, Luyao Li, Zhuanzhuan Chen, Wanwen Yang, Yao Lu, Shuxin Zou, Yuhua Li, Xiaochun Bai
Summary: AML is characterized by self-renewal and differentiation arrest of leukaemia stem cells (LSCs), leading to high relapse rates. The CDK4/6 inhibitor, abemaciclib, has been found to suppress proliferation and promote differentiation of LSCs, and when combined with the Bcl-2 inhibitor venetoclax, it exhibits synergistic anti-leukaemic effects. These findings provide strong rationale for the clinical evaluation of abemaciclib in inducing LSC differentiation and treating aggressive AML and other advanced haematological malignancies.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Multidisciplinary Sciences
Jie Xu, Fan Song, Huijue Lyu, Mikoto Kobayashi, Baozhen Zhang, Ziyu Zhao, Ye Hou, Xiaotao Wang, Yu Luan, Bei Jia, Lena Stasiak, Josiah Hiu-yuen Wong, Qixuan Wang, Qi Jin, Qiushi Jin, Yihao Fu, Hongbo Yang, Ross C. Hardison, Sinisa Dovat, Leonidas C. Platanias, Yarui Diao, Yue Yang, Tomoko Yamada, Aaron D. Viny, Ross L. Levine, David Claxton, James R. Broach, Hong Zheng, Feng Yue
Summary: This study uses Hi-C and whole-genome sequencing to analyze samples from AML patients and healthy donors, revealing recurrent and subtype-specific alterations in chromatin structure and loops. Functional validation and manipulation of DNA methylation further highlight the role of repressive loops and hijacked cis elements in AML.
Article
Multidisciplinary Sciences
Gabriele Casirati, Andrea Cosentino, Adele Mucci, Mohammed Salah Mahmoud, Iratxe Ugarte Zabala, Jing Zeng, Scott B. Ficarro, Denise Klatt, Christian Brendel, Alessandro Rambaldi, Jerome Ritz, Jarrod A. Marto, Danilo Pellin, Daniel E. Bauer, Scott A. Armstrong, Pietro Genovese
Summary: Epitope engineering of donor haematopoietic stem/progenitor cells endows haematopoietic lineages with selective resistance to CAR T cells or monoclonal antibodies, without affecting protein function or regulation, enabling the targeting of genes that are essential for leukaemia survival and reducing the risk of tumour immune escape.
Article
Biochemistry & Molecular Biology
James Hillier, Gemma J. Allcott, Laura A. Guest, Wayne Heaselgrave, Alex Tonks, Myra E. Conway, Amy L. Cherry, Steven J. Coles
Summary: This study provides evidence suggesting that the CXXC motif of cytosolic branched-chain aminotransferase (BCAT1) may contribute to buffering reactive oxygen species (ROS) levels inside acute myeloid leukemia (AML) cells, impacting on ROS-mediated processes in the development of AML.
Article
Multidisciplinary Sciences
Ai Asai-Nishishita, Masahiro Kawahara, Goichi Tatsumi, Masaki Iwasa, Aya Fujishiro, Rie Nishimura, Hitoshi Minamiguchi, Katsuyuki Kito, Makoto Murata, Akira Andoh
Summary: FUS-ERG is a chimeric gene commonly found in MDS and AML with a poor prognosis. This study revealed that AML cells carrying FUS-ERG developed resistance to Aza treatment. RNA sequencing analysis identified genes associated with cell motility, cytokine production, and kinase activity that showed altered expression. Additionally, chromatin organization and transcript variants were found to be involved. Clinical case and whole-genome sequencing results further confirmed the involvement of genes related to FUS-ERG and changes in transcription regulatory factors. It was also discovered that MCL1 inhibitors could partially overcome Aza resistance in FUS-ERG-harbouring AML cells.
SCIENTIFIC REPORTS
(2023)
Article
Oncology
Tamara Rothenburger, Dominique Thomas, Yannick Schreiber, Paul R. Wratil, Tamara Pflantz, Kirsten Knecht, Katie Digianantonio, Joshua Temple, Constanze Schneider, Hanna-Mari Baldauf, Katie-May McLaughlin, Florian Rothweiler, Berna Bilen, Samira Farmand, Denisa Bojkova, Rui Costa, Nerea Ferreiros, Gerd Geisslinger, Thomas Oellerich, Yong Xiong, Oliver T. Keppler, Mark N. Wass, Martin Michaelis, Jindrich Cinatl
Summary: Intrinsic and acquired resistance to CNDAC and related nucleoside analogues are driven by different mechanisms. The lack of cross-resistance between SAMHD1/DCK substrates and non-substrates provides scope for next-line therapies after treatment failure. Understanding the mechanisms behind resistance to CNDAC can help develop more effective treatment strategies for leukemia.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2021)
Article
Oncology
Yang Xiao, Jinghong Chen, Jia Wang, Wei Guan, Mengzhen Wang, Linlin Zhang, Zhiding Wang, Lixin Wang, Li Yu
Summary: In patients with AML, the expression of ICAM-1 is silenced, but the hypomethylating agent can upregulate its expression, facilitating NK cells to kill AML cells. High expression of ICAM-1 can reverse AML immune evasion and activate NK cell function, suggesting a new strategy for AML treatment.
FRONTIERS IN ONCOLOGY
(2021)
Review
Pharmacology & Pharmacy
Heather A. Ogana, Samantha Hurwitz, Nathan Wei, Eliana Lee, Kayla Morris, Karina Parikh, Yong-Mi Kim
Summary: Acute myeloid leukaemia (AML) has a poor prognosis and new therapeutic strategies are needed. The bone marrow (BM) microenvironment contains niches that interact with both normal haematopoietic stem cells and AML cells. Integrins, which are adhesion molecules in the BM microenvironment, play a central role in AML. AML cells express integrins that bind to ligands in the microenvironment, leading to adhesion, intracellular signalling, and drug resistance. Targeting integrins in AML to disrupt interactions with the microenvironment is being explored as a strategy to overcome drug resistance.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Multidisciplinary Sciences
Keith Woodley, Laura S. Dillingh, George Giotopoulos, Pedro Madrigal, Kevin M. Rattigan, Celine Philippe, Vilma Dembitz, Aoife M. S. Magee, Ryan Asby, Louie N. van de Lagemaat, Christopher Mapperley, Sophie C. James, Jochen H. M. Prehn, Konstantinos Tzelepis, Kevin Rouault-Pierre, George S. Vassiliou, Kamil R. Kranc, G. Vignir Helgason, Brian J. P. Huntly, Paolo Gallipoli
Summary: Metabolic rewiring through inhibition of mannose-6-phosphate isomerase sensitizes acute myeloid leukemia (AML) to FLT3-tyrosine kinase inhibitor and standard chemotherapy by enhancing lipid peroxidation and ferroptotic cell death. Resistance to standard and novel therapies in AML is driven by metabolic adaptations, and here the authors identify mannose-6-phosphate isomerase (MPI) inhibition as a sensitizer to cytarabine and FLT3 inhibitors. This metabolic rewiring leads to the activation of the ATF6 arm of the unfolded protein response (UPR), resulting in the accumulation of polyunsaturated fatty acids, lipid peroxidation and ferroptotic cell death in AML cells. These findings emphasize the importance of rewired metabolism in AML therapy resistance and support efforts to sensitize therapy-resistant AML cells to ferroptotic cell death.
NATURE COMMUNICATIONS
(2023)
Article
Hematology
Joana Desterro, Donal P. McLornan, Natalia Curto Garcia, Jennifer O'Sullivan, Samah Alimam, Clodagh Keohane, Claire Woodley, Yvonne Francis, Shahram Kordasti, Deepti H. Radia, Claire N. Harrison
BRITISH JOURNAL OF HAEMATOLOGY
(2019)
Article
Hematology
Nathalie van Leeuwen-Kerkhoff, Theresia M. Westers, Pino J. Poddighe, Tanja D. de Gruijl, Shahram Kordasti, Arjan A. van de Loosdrecht
Article
Surgery
Alberto Sanchez-Fueyo, Gavin Whitehouse, Nathali Grageda, Matthew E. Cramp, Tiong Y. Lim, Marco Romano, Sarah Thirkell, Katie Lowe, Laura Fry, Julie Heward, Alex Kerr, Jakia Ali, Chris Fisher, Gillian Lewis, Andrew Hope, Elisavet Kodela, Mike Lyne, Farzin Farzaneh, Shahram Kordasti, Irene Rebollo-Mesa, Juan Jose Lozano, Niloufar Safinia, Nigel Heaton, Robert Lechler, Marc Martinez-Llordella, Giovanna Lombardi
AMERICAN JOURNAL OF TRANSPLANTATION
(2020)
Review
Pharmacology & Pharmacy
Nahid Zareian, Stefano Aprile, Laura Cristaldi, Mattia Emanuela Ligotti, Sonya Vasto, Farzin Farzaneh
CURRENT PHARMACEUTICAL DESIGN
(2019)
Editorial Material
Immunology
Giuseppina Arboer, Voon H. Ong, Benedetta Costantini, Christopher P. Denton, David Abraham, Leo Placais, Kevin Blighe, Lynne Mithcell, Richard Ellis, Susanne Heck, Paola Nocerino, Trent M. Woodruff, Shahram Kordasti, Claudia Kemper, Dennis E. Hourcade
CELLULAR & MOLECULAR IMMUNOLOGY
(2020)
Article
Immunology
Giovanni A. M. Povoleri, Sylvine Lalnunhlimi, Kathryn J. A. Steel, Shweta Agrawal, Aoife M. O'Byrne, Michael Ridley, Shahram Kordasti, Klaus S. Frederiksen, Ceri A. Roberts, Leonie S. Taams
EUROPEAN JOURNAL OF IMMUNOLOGY
(2020)
Review
Oncology
Susann Winter, Saeed Shoaie, Shahram Kordasti, Uwe Platzbecker
JOURNAL OF CLINICAL ONCOLOGY
(2020)
Article
Cell Biology
Nicola Beucke, Daniela Wesch, Hans-Heinrich Oberg, Christian Peters, Jonas Bochem, Benjamin Weide, Claus Garbe, Graham Pawelec, Susanne Sebens, Christoph Roecken, Hisayoshi Hashimoto, Markus W. Loeffler, Paola Nocerino, Shahram Kordasti, Dieter Kabelitz, Karin Schilbach, Kilian Wistuba-Hamprecht
JOURNAL OF LEUKOCYTE BIOLOGY
(2020)
Article
Hematology
Shok Ping Lim, Benedetta Costantini, Syed A. Mian, Pilar Perez Abellan, Shreyans Gandhi, Marc Martinez Llordella, Juan Jose Lozano, Rita Antunes dos Reis, Giovanni A. M. Povoleri, Thanos P. Mourikis, Ander Abarrategi, Linda Ariza-McNaughton, Susanne Heck, Jonathan M. Irish, Giovanna Lombardi, Judith C. W. Marsh, Dominique Bonnet, Shahram Kordasti, Ghulam J. Mufti
Editorial Material
Hematology
Uwe Platzbecker, Shahram Kordasti
Article
Oncology
Matteo Bersanelli, Erica Travaglino, Manja Meggendorfer, Tommaso Matteuzzi, Claudia Sala, Ettore Mosca, Chiara Chiereghin, Noemi Di Nanni, Matteo Gnocchi, Matteo Zampini, Marianna Rossi, Giulia Maggioni, Alberto Termanini, Emanuele Angelucci, Massimo Bernardi, Lorenza Borin, Benedetto Bruno, Francesca Bonifazi, Valeria Santini, Andrea Bacigalupo, Maria Teresa Voso, Esther Oliva, Marta Riva, Marta Ubezio, Lucio Morabito, Alessia Campagna, Claudia Saitta, Victor Savevski, Enrico Giampieri, Daniel Remondini, Francesco Passamonti, Fabio Ciceri, Niccolo Bolli, Alessandro Rambaldi, Wolfgang Kern, Shahram Kordasti, Francesc Sole, Laura Palomo, Guillermo Sanz, Armando Santoro, Uwe Platzbecker, Pierre Fenaux, Luciano Milanesi, Torsten Haferlach, Gastone Castellani, Matteo G. Della Porta
Summary: The study identified eight distinct subgroups of MDS based on specific genomic features, each with different prognostic outcomes. By integrating clinical and genomic variables, a novel prognostic model was developed to provide personalized survival predictions for MDS patients. This model significantly improved the accuracy of current prognostic tools and has the potential to revolutionize disease classification and prognosis in the future.
JOURNAL OF CLINICAL ONCOLOGY
(2021)
Article
Biology
James W. Opzoomer, Jessica A. Timms, Kevin Blighe, Thanos P. Mourikis, Nicolas Chapuis, Richard Bekoe, Sedigeh Kareemaghay, Paola Nocerino, Benedetta Apollonio, Alan G. Ramsay, Mahvash Tavassoli, Claire Harrison, Francesca Ciccarelli, Peter Parker, Michaela Fontenay, Paul R. Barber, James N. Arnold, Shahram Kordasti
Summary: High-dimensional cytometry is an innovative tool for immune monitoring in health and disease, but analyzing large multiparametric datasets typically requires specialist computational knowledge. ImmunoCluster is an R package designed to aid nonspecialists in immune profiling cellular heterogeneity, providing scalable analysis and visualization tools tailored to users' needs. The framework consists of three core computational stages within an R-based open-source framework.
Article
Oncology
Beth Russell, Charlotte L. Moss, Kieran Palmer, Rushan Sylva, Andrea D'Souza, Harriet Wylie, Anna Haire, Fidelma Cahill, Renee Steel, Angela Hoyes, Isabelle Wilson, Alyson Macneil, Belul Shifa, Maria J. Monroy-Iglesias, Sophie Papa, Sheeba Irshad, Paul Ross, James Spicer, Shahram Kordasti, Danielle Crawley, Kamarul Zaki, Ailsa Sita-Lumsden, Debra Josephs, Deborah Enting, Angela Swampillai, Elinor Sawyer, Paul Fields, David Wrench, Anne Rigg, Richard Sullivan, Mieke Van Hemelrijck, Saoirse Dolly
Summary: The study found that male, Black or Asian ethnicity, and patients with hematological malignancies are at an increased risk of COVID-19. Using cancer patients as the COVID-19 negative comparator group is a major advantage to the study, helping better understand the true impact of COVID-19 on cancer patients.
Letter
Hematology
Jamie Saunders, Natalia Curto-Garcia, Priya Sriskandarajah, Jennifer O'Sullivan, Claire Woodley, Susan Asirvatham, Marion Campbell-Drew, Jonathan Mathias, Tim Ellis, Nona Baker, Deepti H. Radia, Sahra Ali, Shahram Kordasti, Patrick Harrington, Hugues de Lavallade, Donal P. McLornan, Claire N. Harrison
Meeting Abstract
Oncology
Rushan Sylva, Beth Russell, Charlotte Moss, Gincy George, Kieran Palmer, Vallari Shah, Thinzar Ko Ko, Tania Kalsi, Danielle Harari, Luigi De Michele, Shahram Kordasti, Danielle Crawley, Harriet Wylie, Fidelma Cahill, Anna Haire, Andrea D'Souza, Simon Gomberg, Austin Kulasekararaj, Mieke Van Hemelrijck, Saoirse Dolly
CLINICAL CANCER RESEARCH
(2020)