Article
Medicine, Research & Experimental
Juan Ramon Tejedor, Clara Bueno, Meritxell Vinyoles, Paolo Petazzi, Antonio Agraz-Doblas, Isabel Cobo, Raul Torres-Ruiz, Gustavo F. Bayon, Raul F. Perez, Sara Lopez-Tamargo, Francisco Gutierrez-Aguera, Pablo Santamarina-Ojeda, Manuel Ramirez-Orellana, Michela Bardini, Giovanni Cazzaniga, Paola Ballerini, Pauline Schneider, Ronald W. Stam, Ignacio Varela, Mario F. Fraga, Agustin F. Fernandez, Pablo Menendez
Summary: B cell acute lymphoblastic leukemia (B-ALL) is the most common childhood cancer, with infant B-ALL (iB-ALL) showing unique DNA mutational landscape and potential epigenetic mechanisms contributing to leukemogenesis. Integrated analysis of methylome and transcriptome data from MLLr and non-MLLr iB-ALL patients revealed chromatin state alterations and identified distinct gene expression patterns, particularly related to the AP-1 complex and RUNX factors in MLLr iB-ALL. Pharmacological inhibition of AP-1 showed promising potential in impairing MLLr-leukemic growth, suggesting a novel therapeutic approach for MLLr-iB-ALL.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Biochemistry & Molecular Biology
Krzysztof Jedraszek, Marta Malczewska, Karolina Parysek-Wojcik, Monika Lejman
Summary: Despite advances in medicine, acute lymphoblastic leukemia (ALL) remains a challenge for pediatric clinicians due to treatment resistance and disease relapse. This article focuses on B-cell leukemia patients and examines prognostic factors, mechanisms of resistance to therapy, and the impact of genetic factors, including TCF3::HLF translocation. It also compares treatment protocols and explores the resistance of cancer cells to innovative therapies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Sarah Schober, Jennifer M. Rottenberger, Johannes Hilz, Evi Schmid, Martin Ebinger, Tobias Feuchtinger, Rupert Handgretinger, Peter Lang, Manon Queudeville
Summary: The immune environment plays a crucial role in various types of cancer. This study investigates the influence of Th1 cytokines on pediatric acute lymphoblastic leukemia (ALL). The findings suggest that TNF-alpha and IFN-gamma can induce apoptosis in ALL cells, though the reaction varies among different cells. The high expression of IFN-gamma receptor and subsequent activation of STAT1 are correlated with cell death.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2023)
Review
Biochemistry & Molecular Biology
Mateusz Gorecki, Ilona Koziol, Agnieszka Kopystecka, Julia Budzynska, Joanna Zawitkowska, Monika Lejman
Summary: The KMT2A gene is a common target for recurrent translocations in various types of leukemia, and its rearrangement has significant prognostic implications.
Review
Medicine, General & Internal
Hiroto Inaba, Ching-Hon Pui
Summary: Over the past five decades, the outcomes of pediatric acute lymphoblastic leukemia (ALL) have significantly improved, with 5-year survival rates exceeding 90% in high-income countries. The goal for the next decade is to further increase survival towards 100% and minimize treatment-related adverse effects. Genome-wide analyses have allowed for the classification of ALL into various subtypes, with treatment response and minimal residual disease analysis providing insights for new therapeutic strategies.
JOURNAL OF CLINICAL MEDICINE
(2021)
Review
Biochemistry & Molecular Biology
Anca Viorica Ivanov, Mirabela Smaranda Alecsa, Roxana Popescu, Magdalena Iuliana Starcea, Adriana Maria Mocanu, Cristina Rusu, Ingrith Crenguta Miron
Summary: In the past 40 years, the survival rate for pediatric cancer has greatly improved, reaching 75-80%. However, leukemia still remains a major cause of morbidity and mortality in specific patient populations. The future of leukemia treatment lies in molecular therapies, immune therapy, and cellular therapy. Recent advances in the field have led to the development of novel therapies for childhood leukemia, including targeted therapies and immunotherapies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Medicine, General & Internal
Jae Won Yoo, Ari Ahn, Jong-Mi Lee, Suejung Jo, Seongkoo Kim, Jae Wook Lee, Bin Cho, Yonggoo Kim, Myungshin Kim, Nack-Gyun Chung
Summary: This study investigated the mutational spectrum in pediatric acute lymphoblastic leukemia (ALL) in Korea using next-generation sequencing (NGS) technology. The most frequently mutated genes and pathways were identified in B-cell ALL and T-cell ALL, and several pairs of co-occurring mutations were found. The study also revealed the most frequent newly emerged mutation in relapsed ALL.
JOURNAL OF CLINICAL MEDICINE
(2022)
Review
Oncology
Thai Hoa Tran, Stephen P. Hunger
Summary: Acute lymphoblastic leukemia (ALL) is the most common childhood cancer and has shown significant improvement in survival rates through risk-adapted chemotherapy, prevention measures, and molecular analysis. However, challenges remain for older patients and relapsed/refractory cases.
SEMINARS IN CANCER BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Shawn H. R. Lee, Wenjian Yang, Yoshihiro Gocho, August John, Lauren Rowland, Brandon Smart, Hannah Williams, Dylan Maxwell, Jeremy Hunt, Wentao Yang, Kristine R. R. Crews, Kathryn G. G. Roberts, Sima Jeha, Cheng Cheng, Seth E. E. Karol, Mary V. V. Relling, Gary L. L. Rosner, Hiroto Inaba, Charles G. G. Mullighan, Ching-Hon Pui, William E. E. Evans, Jun J. J. Yang
Summary: Contemporary chemotherapy for childhood acute lymphoblastic leukemia is personalized based on clinical features, leukemia genomics, and minimal residual disease. However, the pharmacological basis of these prognostic variables is unclear. A study analyzing samples from 805 children with newly diagnosed leukemia identified variations in drug response and determined that certain subtypes were more sensitive to specific agents. The findings suggest opportunities for individualizing therapy and exploring alternative strategies for childhood acute lymphoblastic leukemia.
Review
Cell Biology
Jing Wang, Pei Huang, Changhui Lang, Yan Luo, Zhixu He, Yan Chen
Summary: Trace elements are important substances with low content in the human body and changes in their levels are related to diseases. This paper focuses on their relationship with acute lymphoblastic leukemia (ALL), a malignant blood tumor. Both the trace element levels in ALL patients and the efficacy of different treatment methods are linked to the corresponding trace element changes. It is believed that the abnormal metabolism of trace elements in the body is related to ALL, and this paper aims to provide more information on trace elements for the diagnosis, treatment, and prevention of ALL.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Genetics & Heredity
Zeljko Antic, Stefan H. Lelieveld, Cedric G. van der Ham, Edwin Sonneveld, Peter M. Hoogerbrugge, Roland P. Kuiper
Summary: Investigating mutations in clusters separated in time may help understand mutational mechanisms and discover underlying causes.
Review
Cell Biology
Huan Xu, Hui Yu, Runming Jin, Xiaoyan Wu, Hongbo Chen
Summary: Acute lymphoblastic leukemia is characterized by genetic and epigenetic abnormalities, with epigenetic mechanisms playing a significant role in leukemogenesis. Compared to genetic alterations, epigenetic abnormalities are relatively reversible with small molecule-based agents.
Article
Oncology
Jonathan D. Diedrich, Qian Dong, Daniel C. Ferguson, Brennan P. Bergeron, Robert J. Autry, Maoxiang Qian, Wenjian Yang, Colton Smith, James B. Papizan, Jon P. Connelly, Kohei Hagiwara, Kristine R. Crews, Shondra M. Pruett-Miller, Ching-Hon Pui, Jun J. Yang, Mary V. Relling, William E. Evans, Daniel Savic
Summary: The study reveals extensive chromatin reprogramming in ALL, with subtype-specific chromatin landscapes modulated by genetic variation. Differences in chromatin accessibility between ALL and normal B-cells suggest activation of repressed chromatin domains and disruption of normal B-cell development in ALL.
Review
Biochemistry & Molecular Biology
Chana L. Glasser, Jing Chen
Summary: The treatment for relapsed acute lymphoblastic leukemia (ALL) in children and young adults is constantly evolving. Immunotherapy has revolutionized the field by harnessing the patient's immune system to target and eliminate leukemia cells. Novel immunotherapies, such as blinatumomab, inotuzumab, daratumomab, and chimeric antigen receptor T-cell therapy, show promising potential to enhance outcomes while reducing toxicity.
Article
Oncology
Anke Barnbrock, Natalia Luesebrink, Susanne Schubert-Bast, Konrad Bochennek, Thomas Lehrnbecher
Summary: The purpose of this study was to evaluate the prognostic benefit of electroencephalogram (EEG) performed during initial work-up of children with newly diagnosed acute lymphoblastic leukemia (ALL). The study found that EEG has no predictive value in determining the occurrence and etiology of neurological complications in pediatric patients with ALL.
SUPPORTIVE CARE IN CANCER
(2023)
Article
Biochemistry & Molecular Biology
Peng Huang, Jesper S. Hansen, Karim H. Saba, Anna Bergman, Florentina Negoita, Pontus Gourdon, Anna Hagstrom-Andersson, Karin Lindkvist-Petersson
Summary: Aquaporins play a crucial role in maintaining water homeostasis in the human body, and recent studies have shown the physiological importance of aquaporins as glycerol channels. In addition to aquaglyceroporins, the discovery of AQP1 in human primary adipocytes suggests a role in response to hyperosmotic stress. The coordination of aquaglyceroporins and perilipin 1 in human adipocytes contributes to the homeostasis of glycerol and water during fasting and feeding.
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
(2022)
Article
Oncology
Henrik Lilljebjorn, Christina Orsmark-Pietras, Felix Mitelman, Anna Hagstrom-Andersson, Thoas Fioretos
Summary: Transcriptional profiling of acute leukemia through RNA-sequencing has greatly contributed to our understanding of the disease and has the potential to improve clinical diagnostics and precision medicine for acute leukemia.
SEMINARS IN CANCER BIOLOGY
(2022)
Review
Urology & Nephrology
Marc Ghannoum, Darren M. Roberts, David S. Goldfarb, Jesper Heldrup, Kurt Anseeuw, Tais F. Galvao, Thomas D. Nolin, Robert S. Hoffman, Valery Lavergne, Paul Meyers, Sophie Gosselin, Tudor Botnaru, Karine Mardini, David M. Wood, EXTRIP Workgrp
Summary: In the management of methotrexate toxicity, there is still controversy over the utility of extracorporeal treatments. Existing evidence supports not recommending extracorporeal treatments when glucarpidase is not administered, and also not recommending extracorporeal treatments when glucarpidase is administered, with a stronger recommendation for glucarpidase treatment in severe methotrexate toxicity.
CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
(2022)
Article
Oncology
Bradford J. Siegele, Anat O. Stemmer-Rachamimov, Henrik Lilljebjorn, Thoas Fioretos, Amanda C. Winters, Paola Dal Cin, Amy Treece, Alisa Gaskell, Valentina Nardi
Summary: The expression of the DUX4 oncoprotein detected by immunohistochemistry can serve as a surrogate for molecular detection of DUX4 fusions in B-ALL. This finding provides a new approach to subclassify B-ALL and improve understanding of its subtypes.
GENES CHROMOSOMES & CANCER
(2022)
Article
Oncology
Signe Modvig, Rasmus Wernersson, Nina Friesgaard obro, Lars Ronn Olsen, Claus Christensen, Susanne Rosthoj, Matilda Degn, Gitte Wullf Jurgensen, Hans O. Madsen, Birgitte Klug Albertsen, Peder Skov Wehner, Steen Rosthoj, Henrik Lilljebjorn, Thoas Fioretos, Kjeld Schmiegelow, Hanne Vibeke Marquart
Summary: The study showed that a CD34-negative immunophenotype is considered a good prognostic factor in BCP-ALL patients, while high CD34 expression is associated with poor therapy response and an altered gene expression profile reminiscent of migrating cancer stem-like cells.
MOLECULAR ONCOLOGY
(2022)
Article
Oncology
Milad Abolhalaj, Viktor Sincic, Henrik Lilljebjorn, Carl Sanden, Alar Aab, Karin Hagerbrand, Peter Ellmark, Carl A. K. Borrebaeck, Thoas Fioretos, Kristina Lundberg
Summary: The study revealed altered transcriptional profiles in different T-cell subpopulations from TP53-mutated AML patients compared to healthy controls. Both CTLs and Tregs in TP53-mutated AML showed stronger IFN-alpha and IFN-gamma signaling. Tregs in TP53-mutated AML displayed gene expression patterns suggesting metabolic adaptation, while CTLs exhibited features of exhaustion/dysfunction with increased expression of TIM3 and enrichment of exhaustion-related gene set.
Editorial Material
Pharmacology & Pharmacy
Maria Teresa Esposito, Anna Hagstroem-Andersson, Ronald W. Stam, Stefania Bortoluzzi
FRONTIERS IN PHARMACOLOGY
(2022)
Letter
Hematology
Helena Agerstam, Henrik Lilljebjorn, Marianne Rissler, Carl Sanden, Thoas Fioretos
Article
Oncology
Srinivas Veerla, Lennart Hohmann, Deborah F. Nacer, Johan Vallon-Christersson, Johan Staaf
Summary: PAM50 gene expression subtypes play a crucial role in the molecular classification of breast cancer and are closely related to the tumor's underlying clinical subgroup. This study demonstrates the dependence of PAM50 nearest-centroid classification on biological processes within and across ER/PR/HER2 subgroups and PAM50 subtypes. Understanding the commonly used PAM50 subtyping scheme helps in interpreting breast tumors with conflicting PAM50 classification compared to clinical biomarkers.
Article
Hematology
Maria Rodriguez-Zabala, Ramprasad Ramakrishnan, Katrin Reinbach, Somadri Ghosh, Leal Oburoglu, Antoni Falques-Costa, Kishan Bellamkonda, Mats Ehinger, Pablo Pena-Martinez, Noelia Puente-Moncada, Henrik Lilljebjorn, Jorg Cammenga, Cornelis Jan Pronk, Vladimir Lazarevic, Thoas Fioretos, Anna K. Hagstrom-Andersson, Niels-Bjarne Woods, Marcus Jaras
Summary: Acute myeloid leukemia (AML) is driven by leukemia stem cells (LSCs) which are resistant to therapy. This study identified GLUT1 as a critical metabolic dependency for LSCs and showed that its disruption can suppress leukemia progression and improve survival. Inhibition of GLUT1 leads to metabolic reprogramming, increased apoptosis and autophagic activity. Dual inhibition of GLUT1 and oxidative phosphorylation exhibited synergistic effects against AML.
Article
Hematology
Sofia von Palffy, Hanna Thorsson, Pablo Pena-Martinez, Noelia Puente-Moncada, Carl Sanden, Anna M. Blom, Rasmus Henningsson, Gunnar Juliusson, Ben King, Niklas Landberg, Vladimir Lazarevic, Christina Orsmark-Pietras, Marianne Rissler, Vendela Rissler, Helena Agerstam, Marcus Jaras, Henrik Lilljebjorn, Thoas Fioretos
Summary: Mutations in the NPM1 gene are common in acute myeloid leukemia (AML), but relapse is still a significant concern. In this study, we identified the complement receptor C3AR as specifically expressed in NPM1-mutated AML cells, making it a potential target for antibody-based therapies. We also found that C3AR, in combination with GPR56, distinguishes leukemic stem cells from normal hematopoietic stem cells, and stimulation of C3AR-expressing cells leads to increased survival of AML cells. Furthermore, antibodies directed against C3AR effectively induce natural killer cell-mediated killing of primary AML cells, highlighting its potential as a therapeutic target in NPM1-mutated AML.
Article
Hematology
Mattias Pilheden, Louise Ahlgren, Axel Hyrenius-Wittsten, Veronica Gonzalez-Pena, Helena Sturesson, Hanne Vibeke Hansen Marquart, Birgitte Lausen, Anders Castor, Cornelis Jan Pronk, Gisela Barbany, Katja Pokrovskaja Tamm, Linda Fogelstrand, Olli Lohi, Ulrika Noren-Nystrom, Johanna Asklin, Yilun Chen, Guangchun Song, Michael Walsh, Jing Ma, Jinghui Zhang, Lao H. Saal, Charles Gawad, Anna K. Hagstrom-Andersson
Summary: Infants and children with KMT2A-gene rearrangements in acute lymphoblastic leukemia (ALL) often carry low-frequency cancer-associated mutations, indicating a wide subclonal genetic landscape.
Article
Biochemistry & Molecular Biology
Jacob Karlstrom, Mattias Aine, Johan Staaf, Srinivas Veerla
Summary: The study introduces a novel unsupervised clustering method called SRIQ, which can address some issues in commonly used unsupervised analysis methods. Using RNA sequencing data from lung adenocarcinomas, the technical reproducibility and performance of SRIQ are demonstrated and compared to the commonly used consensus clustering method. With differential gene expression analysis and auxiliary molecular data, SRIQ is able to define new tumor subsets that are biologically relevant and consistent with existing subtypes.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2022)