Review
Immunology
Shanie Saghafian-Hedengren, Eva Sverremark-Ekstrom, Anna Nilsson
Summary: The article summarizes the role of the immune system in recognizing and eliminating malignant cells, and discusses the potential challenges faced by T-cell immunotherapies targeting pediatric cancers in early life stages.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Medicine, Research & Experimental
Yizhen Li, Wentao Yang, Meenakshi Devidas, Stuart S. Winter, Chimene Kesserwan, Wenjian Yang, Kimberly P. Dunsmore, Colton Smith, Maoxiang Qian, Xujie Zhao, Ranran Zhang, Julie M. Gastier-Foster, Elizabeth A. Raetz, William L. Carroll, Chunliang Li, Paul P. Liu, Karen R. Rabin, Takaomi Sanda, Charles G. Mullighan, Kim E. Nichols, William E. Evans, Ching-Hon Pui, Stephen P. Hunger, David T. Teachey, Mary Relling, Mignon L. Loh, Jun J. Yang
Summary: Genetic alterations in the RUNX1 gene are associated with various blood disorders, especially those of the megakaryocyte and myeloid lineages. Germline RUNX1 variants have different effects on B-ALL and T-ALL, with the latter showing severe damaging effects. Additionally, JAK3 mutation is a common somatic genomic abnormality in T-ALL with germline RUNX1 variants.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Biochemistry & Molecular Biology
Keren Xu, Shaobo Li, Priyatama Pandey, Alice Y. Kang, Libby M. Morimoto, Nicholas Mancuso, Xiaomei Ma, Catherine Metayer, Joseph L. Wiemels, Adam J. de Smith
Summary: This study investigated whether DNA methylation mediates the effect of genetic risk loci for childhood ALL. The researchers found that DNA methylation at CpG cg01139861 mediated the effects of the IKZF1 risk SNP rs78396808, with a significant mediation effect in Latinos.
HUMAN MOLECULAR GENETICS
(2022)
Article
Hematology
Yizhen Li, Xu Yang, Yu Sun, Zhenhua Li, Wenjian Yang, Bensheng Ju, John Easton, Deqing Pei, Cheng Cheng, Shawn Lee, Ching-Hon Pui, Jiyang Yu, Hongbo Chi, Jun J. Yang
Summary: T-cell immunity plays a pivotal role in maintaining long-term remission of acute lymphoblastic leukemia (ALL) and the interplay between host immunity and drug resistance can be harnessed to improve chemotherapy outcomes for ALL.
Article
Oncology
Sofiane Berrazouane, Alexie Doucet, Marc Boisvert, Frederic Barabe, Fawzi Aoudjit
Summary: Cell adhesion to VCAM-1 via the VLA-4 receptor induces chemoresistance in T-ALL cells by activating PYK2, leading to doxorubicin efflux. In contrast, adhesion to fibronectin via VLA-5 does not affect doxorubicin resistance, highlighting the potential of targeting the VLA-4/PYK2 pathway to overcome chemoresistance in T-ALL and reduce relapse risk.
Article
Pathology
Chih-Hsiang Yu, Gang Wu, Chia-Ching Chang, Shiann-Tarng Jou, Meng-Yao Lu, Kai-Hsin Lin, Shu-Huey Chen, Kang-Hsi Wu, Chao-Neng Cheng, Fang-Liang Huang, Chao-Neng CHeng, Hsiu-Hao Chang, Dale Hedges, Jinn-Li Wang, Hsiu-Ju Yen, Meng-Ju Li, Shu-Wei Chou, Chen-Ting Hung, Ze-Shiang Lin, Chien-Yu Lin, Hsuan-Yu Chen, Yu-Ling Ni, Yin-Chen Hsu, Dong-Tsamn Lin, Shu-Wha Lin, Jun J. Yang, Ching-Hon Pui, Sung-Liang Yu, Yung-Li Yang
Summary: Identification of specific leukemia subtypes is crucial for risk-directed therapy in childhood acute lymphoblastic leukemia (ALL). Although RNA sequencing (RNA-seq) is the most effective method, its routine use is expensive in resource-limited countries. This study enrolled 295 pediatric ALL patients and used a combination of screening methods and RNA-seq to improve classification and clinical assessment of childhood ALL.
JOURNAL OF MOLECULAR DIAGNOSTICS
(2022)
Review
Oncology
Marina Oldenburg, Nadine Ruechel, Stefan Janssen, Arndt Borkhardt, Katharina L. Goessling
Summary: The concept of holobionts emphasizes the complex interactions between a host and other species, which, if disturbed may lead to disease and premature aging. The impact of chemotherapy on the microbiome and long-term dysbiosis in survivors of acute lymphoblastic leukemia requires further research.
Article
Cell Biology
Yuting Zhu, Xiaopeng Ma, Heng Zhang, Yijun Wu, Meiyun Kang, Yongjun Fang, Yao Xue
Summary: The study revealed that circADD2 is down-regulated in ALL, and its overexpression inhibits cell proliferation while promoting apoptosis. circADD2 functions by directly sponging miR-149-5p.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Oncology
Shawn H. R. Lee, Zhenhua Li, Evelyn H. Z. Lim, Winnie H. N. Chin, Nan Jiang, Kean Hui Chiew, Zhiwei Chen, Bernice L. Z. Oh, Ah Moy Tan, Hany Ariffin, Jun J. Yang, Allen E. J. Yeoh
Summary: The aim of this study was to investigate the association between T-cell receptor (TCR) repertoire diversity and the risk of allergy. The study found that patients with a more diverse and dynamically changing TCR repertoire had an increased risk of allergy and decreased asparaginase activity. A higher variability of the repertoire between timepoints predicted the occurrence of allergy. After allergy occurred, the TCR repertoire became more similar. Understanding the immunological basis of this common toxicity in childhood acute lymphoblastic leukemia (ALL) can help in developing better methods to predict or manage this event.
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)
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
Biochemistry & Molecular Biology
Alvaro Martinez-Rubio, Salvador Chulian, Cristina Blazquez Goni, Manuel Ramirez Orellana, Antonio Perez Martinez, Alfonso Navarro-Zapata, Cristina Ferreras, Victor M. Perez-Garcia, Maria Rosa
Summary: CAR T-cell therapy shows high response rates in treating B-cell Acute Lymphoblastic Leukemia, but relapse can still occur. The status of CAR T cells in bone marrow plays a key role in treatment response. A mathematical model depicting interactions between different cell populations is essential in understanding the causes of treatment resistance.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Medicine, General & Internal
Maria Kourti, Michalis Aivaliotis, Emmanouel Hatzipantelis
Summary: Acute lymphoblastic leukemia (ALL) is the most common cancer in children, and risk-directed therapy based on clinical, biologic and genetic features has played a significant role in its treatment. Despite improvement in survival rates, ALL remains a leading cause of cancer-related deaths. Proteomics is a cutting-edge technology that aims to understand the impact of the proteome on leukemia subtypes and identify new biomarkers and targets for therapy.
Article
Oncology
Marco Severgnini, Mariella D'Angio, Silvia Bungaro, Giovanni Cazzaniga, Ingrid Cifola, Grazia Fazio
Summary: In this study, RNA-seq technology was used to comprehensively profile the transcriptional landscape of childhood BCP-ALL cases. The analysis revealed a subset of conjoined genes (CGs) that were exclusively expressed in leukemic cases, suggesting a potential novel mechanism of transcriptional regulation in childhood leukemia and potential leukemia-specific biomarkers.
Article
Oncology
Maxime Caru, Caroline Laverdiere, Valerie Lemay, Simon Drouin, Laurence Bertout, Maja Krajinovic, Gregor Andelfinger, Daniel Sinnett, Daniel Curnier
Summary: The study demonstrated that childhood ALL survivors exposed to chemotherapy can achieve a safe maximal CPET without long-term complications. Regression analysis showed a significant association between the cumulative dose of doxorubicin and VO(2)peak.
SUPPORTIVE CARE IN CANCER
(2021)
Editorial Material
Hematology
Rosanna Ghinai, Judit Sutak, Moin Saleem, John Moppett
BRITISH JOURNAL OF HAEMATOLOGY
(2020)
Article
Oncology
Nobuko Hijiya, C. Michel Zwaan, Carmelo Rizzari, Robin Foa, Floor Abbink, Donna Lancaster, Judith Landman-Parker, Frederic Millot, John Moppett, Brigitte Nelken, Maria Caterina Putti, Xianbin Tian, Karen Sinclair, Helene Santanastasio, Aby Buchbinder, Pamela Kearns
CLINICAL CANCER RESEARCH
(2020)
Article
Hematology
Amir Enshaei, David O'Connor, Jack Bartram, Jeremy Hancock, Christine J. Harrison, Rachael Hough, Sujith Samarasinghe, Monique L. den Boer, Judith M. Boer, Hester A. de Groot-Kruseman, Hanne V. Marquart, Ulrika Noren-Nystrom, Kjeld Schmiegelow, Claire Schwab, Martin A. Horstmann, Gabriele Escherich, Mats Heyman, Rob Pieters, Ajay Vora, John Moppett, Anthony V. Moorman
Article
Oncology
Nirali N. Shah, Deepa Bhojwani, Keith August, Andre Baruchel, Yves Bertrand, Jessica Boklan, Luciano Dalla-Pozza, Robyn Dennis, Nobuko Hijiya, Franco Locatelli, Paul L. Martin, Francoise Mechinaud, John Moppett, Susan R. Rheingold, Claudine Schmitt, Tanya M. Trippett, Meina Liang, Kemal Balic, Xia Li, Inna Vainshtein, Nai Shun Yao, Ira Pastan, Alan S. Wayne
PEDIATRIC BLOOD & CANCER
(2020)
Article
Multidisciplinary Sciences
Matthew Bashton, Robin Hollis, Sarra Ryan, Claire J. Schwab, John Moppett, Christine J. Harrison, Anthony V. Moorman, Amir Enshaei
SCIENTIFIC REPORTS
(2020)
Article
Hematology
Paraskevi Diamanti, Benjamin C. Ede, Phoebe E. Dace, William J. Barendt, Charlotte Cox, Jeremy P. Hancock, John P. Moppett, Allison Blair
Summary: Relapse of paediatric acute lymphoblastic leukaemia (ALL) may occur due to the persistence of resistant cells with leukaemia-propagating ability (LPC). Response to BCL-2 inhibitors navitoclax and venetoclax varies in LPC subpopulations from B-cell precursor (BCP) and T-cell ALL cases, with navitoclax showing more efficacy. Some LPC are resistant to BCL-2 inhibitors, indicating the need for combination therapy with other therapeutics for sustained remission.
BRITISH JOURNAL OF HAEMATOLOGY
(2021)
Article
Hematology
Anthony V. Moorman, Claire Schwab, Emily Winterman, Jerry Hancock, Anna Castleton, Michelle Cummins, Brenda Gibson, Nick Goulden, Pam Kearns, Beki James, Amy A. Kirkwood, Donna Lancaster, Mabrouk Madi, Andrew McMillan, Jayashree Motwani, Alice Norton, Aengus O'Marcaigh, Katharine Patrick, Neha Bhatnagar, Amrana Qureshi, Deborah Richardson, Simone Stokley, Gordon Taylor, Frederik W. van Delft, John Moppett, Christine J. Harrison, Sujith Samarasinghe, Ajay Vora
BRITISH JOURNAL OF HAEMATOLOGY
(2020)
Letter
Hematology
Giorgio Ottaviano, Susan Baird, Denise Bonney, Philip Connor, Michelle Cummins, Pamela Evans, Brenda Gibson, Rachel Hough, Danielle Ingham, Anne Kelly, Amrana Qureshi, Donna Lancaster, John Moppett, Alice Norton, Jeanette Payne, Simone Stockley, Sara Ghorashian, Persis Amrolia, Waseem Qasim, Ajay Vora
BRITISH JOURNAL OF HAEMATOLOGY
(2021)
Article
Oncology
Thomas Creasey, Amir Enshaei, Karin Nebral, Claire Schwab, Kathryn Watts, Gavin Cuthbert, Ajay Vora, John Moppett, Christine J. Harrison, Adele K. Fielding, Oskar A. Haas, Anthony V. Moorman
Summary: This study found that low hypodiploidy (HoTr) is more common and has a worse prognosis in adults with ALL than previously estimated. By using SNP array analysis, accurate classification and prediction of chromosomal status in ALL patients can be achieved.
GENES CHROMOSOMES & CANCER
(2021)
Article
Multidisciplinary Sciences
Rachel A. Smith, Tosti J. Mankelow, Despoina Drizou, Thomas Bullock, Tom Latham, Sara Trompeter, Allison Blair, David J. Anstee
Summary: Sickle cell disease (SCD) is a common genetic disorder characterized by the presence of various red cell-derived particles (RCDP) in the plasma, which are decorated with prothrombotic phosphatidylserine (PS) and contribute significantly to hypercoagulation.
SCIENTIFIC REPORTS
(2021)
Article
Hematology
Paraskevi Diamanti, Charlotte Cox, Benjamin C. Ede, Robert A. Uger, John P. Moppett, Allison Blair
Summary: The study found that CD200 could be an attractive target for treating low-risk ALL, and experiments conducted in vitro and in vivo confirmed that targeted therapy with the monoclonal antibody TTI-CD200 is effective for CD200(+) LPCs.
Editorial Material
Hematology
John Moppett
BRITISH JOURNAL OF HAEMATOLOGY
(2022)
Article
Oncology
Anthony V. Moorman, Grace Antony, Rachel Wade, Ellie R. Butler, Amir Enshaei, Christine J. Harrison, John Moppett, Rachael Hough, Clare Rowntree, Jeremy Hancock, Nicholas Goulden, Sujith Samarasinghe, Ajay Vora
Summary: The long-term outcomes of the UKALL2003 trial confirmed that treatment intensity can be adjusted based on minimal residual disease (MRD) stratification for patients with acute lymphoblastic leukemia. Low-risk patients can safely de-escalate therapy, while intensified therapy benefits high-risk patients. The time to cure is similar across risk groups.
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Article
Multidisciplinary Sciences
Benjamin C. Ede, Paraskevi Diamanti, David S. Williams, Allison Blair
Summary: The study developed non-toxic, biodegradable Dex-loaded nanovectors to extend drug exposure and distribution in vivo, showing efficacy comparable to free drug. Notably, the study achieved this without the need for high levels of DMSO solvent in the formulation.
SCIENTIFIC REPORTS
(2021)