Article
Oncology
Marcin Braun, Agata Pastorczak, Lukasz Sedek, Joanna Taha, Joanna Madzio, Izabela Jatczak-Pawlik, Kamila Wypyszczak, Michal Matysiak, Katarzyna Derwich, Monika Lejman, Bernarda Kazanowska, Tomasz Szczepanski, Jerzy R. Kowalczyk, Wojciech Mlynarski
Summary: The presence of minimal residual disease (MRD) and specific molecular abnormalities, such as IKZF1 gene aberrations, are strong predictors of outcome in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL). A recently-defined IKZF1-plus microdeletion profile can provide additional predictive value for treatment outcome in childhood BCP-ALL and contribute to more efficient patient stratification.
HEMATOLOGICAL ONCOLOGY
(2022)
Article
Hematology
Hiroyuki Kimura, Masahiro Onozawa, Shota Yoshida, Naoki Miyashita, Shota Yokoyama, Toshihiro Matsukawa, Shinsuke Hirabayashi, Hideki Goto, Tomoyuki Endo, Satoshi Oguri, Shinichi Fujisawa, Akio Mori, Takeshi Kondo, Daisuke Hidaka, Kohei Okada, Shuichi Ota, Yasutaka Kakinoki, Yutaka Tsutsumi, Satoshi Yamamoto, Takuto Miyagishima, Junichi Hashiguchi, Takahiro Nagashima, Makoto Ibata, Kentaro Wakasa, Yoshihito Haseyama, Katsuya Fujimoto, Toshimichi Ishihara, Hajime Sakai, Takanori Teshima
Summary: IKZF1 deletion is a common genomic alteration in B-cell acute lymphoblastic leukemia (B-ALL), which can be categorized into dominant-negative (DN) and loss of function (LOF) deletions. A retrospective analysis of 117 adult B-ALL patients revealed that the specific type of deletion impacts the prognosis. Patients with at least one allele of increment 4-7 belonged to the DN group, and they exhibited significantly higher overall survival than the LOF and wildtype (WT) groups.
ANNALS OF HEMATOLOGY
(2023)
Article
Pharmacology & Pharmacy
Raffaella Franca, Gabriele Stocco, Valentina Kiren, Antimo Tessitore, Franca Fagioli, Paola Quarello, Nicoletta Bertorello, Carmelo Rizzari, Antonella Colombini, Laura Rachele Bettini, Franco Locatelli, Luciana Vinti, Katia Girardi, Daniela Silvestri, Maria Grazia Valsecchi, Giuliana Decorti, Marco Rabusin
Summary: In the maintenance phase of the AIEOP-BFM ALL protocol, adjustments of mercaptopurine dosage are made based on the white blood cell count of patients. However, the concentration and variation of MP metabolites were found to have no direct impact on relapse, while children in the intermediate risk group had a higher risk of relapse. Understanding the mechanism behind the PACSIN2 rs2413739 genotype and its effect on outcomes requires further research.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Hematology
Zhenhua Li, Ti-Cheng Chang, Jacob J. Junco, Meenakshi Devidas, Yizhen Li, Wenjian Yang, Xin Huang, Dale J. Hedges, Zhongshan Cheng, Mary Shago, Andrew J. Carroll, Nyla A. Heerema, Julie Gastier-Foster, Brent L. Wood, Michael J. Borowitz, Lauren Sanclemente, Elizabeth A. Raetz, Stephen P. Hunger, Eleanor Feingold, Tracie C. Rosser, Stephanie L. Sherman, Mignon L. Loh, Charles G. Mullighan, Jiyang Yu, Gang Wu, Philip J. Lupo, Karen R. Rabin, Jun J. Yang
Summary: This study investigates the genomics of Down syndrome-related acute lymphoblastic leukemia (DS-ALL) and identifies 15 molecular subtypes, as well as abnormal activation of key genes. It also reveals the common occurrence of somatic genomic abnormalities mediated by gene rearrangements in DS-ALL and the association between subtype heterogeneity and prognosis. These findings provide important insights into the biology of DS-ALL and offer opportunities for individualized treatment.
Review
Hematology
Shyam Srinivasan, Subramaniam Ramanathan, Shathish Kumar, Srinivasan Peyam, Venkatraman Radhakrishnan
Summary: IKZF1 alteration is an essential regulator in childhood acute lymphoblastic leukemia with negative impact on prognosis. This meta-analysis examines the prevalence and prognostic significance of IKZF1 deletion in childhood ALL and highlights its association with poor survival outcomes.
ANNALS OF HEMATOLOGY
(2023)
Article
Oncology
Maria Sara Felice, Patricia Laura Rubio, Jorge Digiorge, Mariangeles Barreda Frank, Celeste Sabrina Martinez, Myriam Ruth Guitter, Elisa Olga Sajaroff, Cristian German Sanchez La Rosa, Carla Luciana Pennella, Luisina Belen Peruzzo, Maria Alejandra Deu, Elizabeth Melania Alfaro, Maria Constanza Guardia, Gladys Gutierrez, Maria Angelica Fernandez Barbieri, Ezequiel Recondo, Maria Soledad Vides Herrera, Vanina Livio, Constanza Arnaiz, Carolina Romero, Cristina Noemi Alonso, Jorge Gabriel Rossi
Summary: Deletions in the IKZF1 gene have been associated with poor prognosis in ALL. The co-occurrence of these deletions with deletions in other genes appears to better define prognosis. The study shows that the status of IKZF1 can influence the survival of pediatric ALL patients, especially in those with intermediate risk.
Review
Medicine, General & Internal
Ilaria Iacobucci, Shunsuke Kimura, Charles G. Mullighan
Summary: Acute lymphoblastic leukemia (ALL) has achieved cure rates exceeding 90% in children, but remains a leading cause of cancer-related death in the young. Next generation sequencing has led to significant advances in understanding leukemogenesis and the development of novel therapeutic approaches, including mutation-specific and mutation-agnostic treatments.
JOURNAL OF CLINICAL MEDICINE
(2021)
Review
Oncology
Yang Song, Qiuyun Fang, Yingchang Mi
Summary: This review primarily discusses the most prevalent CNVs in B-ALL, aiming to elucidate their clinical value and the importance of personalized management.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Wenxiang Sun, Jingtao Guo, David McClellan, Alexandra Poeschla, Diana Bareyan, Mattie J. Casey, Bradley R. Cairns, Dean Tantin, Michael E. Engel
Summary: GFI1 and IKAROS cooperate to regulate the expression of hallmark T-cell development genes in T-acute lymphoblastic leukemia (ALL) cells. NOTCH3, a key factor in T-ALL pathogenesis, is transactivated by GFI1 and IKAROS. The SNAG domain of GFI1 plays an important role in this process.
MOLECULAR CANCER RESEARCH
(2022)
Article
Medicine, General & Internal
Mirella Ampatzidou, Stefanos I. Papadhimitriou, Anna Paisiou, Georgios Paterakis, Marianna Tzanoudaki, Vassilios Papadakis, Lina Florentin, Sophia Polychronopoulou
Summary: A Greek cohort study of pediatric ALL demonstrated that the deletion of the CDKN2A/2B gene is associated with poor prognosis, with biallelic deletions showing the worst outcomes. The study findings suggest that CDKN2A/2B deletions can further stratify existing risk groups, identifying patient subgroups with different outcomes.
Article
Oncology
Mirella Ampatzidou, Lina Florentin, Vassilios Papadakis, Georgios Paterakis, Marianna Tzanoudaki, Dimitra Bouzarelou, Stefanos Papadhimitriou, Sophia Polychronopoulou
Summary: Recent genomic analyses in acute lymphoblastic leukemia have identified CNAs as potential risk stratification markers, with novel prognostic value in patient outcome. The proposed CNA-profile risk index demonstrates significant differences in event-free survival rates, showing feasibility in BFM-based protocols to refine risk stratification and predict patient outcomes.
Article
Oncology
Jan-Niklas Eckardt, Sebastian Stasik, Christoph Roellig, Andreas Petzold, Tim Sauer, Sebastian Scholl, Andreas Hochhaus, Martina Crysandt, Tim H. Bruemmendorf, Ralph Naumann, Bjoern Steffen, Volker Kunzmann, Hermann Einsele, Markus Schaich, Andreas Burchert, Andreas Neubauer, Kerstin Schaefer-Eckart, Christoph Schliemann, Stefan W. Krause, Regina Herbst, Mathias Haenel, Maher Hanoun, Ulrich Kaiser, Martin Kaufmann, Zdenek Racil, Jiri Mayer, Uta Oelschlaegel, Wolfgang E. Berdel, Gerhard Ehninger, Hubert Serve, Carsten Mueller-Tidow, Uwe Platzbecker, Claudia D. Baldus, Andreas Dahl, Johannes Schetelig, Martin Bornhaeuser, Jan Moritz Middeke, Christian Thiede
Summary: Genetic lesions of IKZF1 are frequent events and well-established markers of adverse risk in acute lymphoblastic leukemia. However, their function in the pathophysiology and impact on patient outcome in acute myeloid leukemia (AML) remains elusive. We found that AML with mutated IKZF1 was associated with alterations in other genes and had a poor prognosis. Mutated IKZF1 was an independent marker of adverse risk and affected the treatment outcomes and survival rates of AML patients, even those who underwent allogeneic hematopoietic stem cell transplantation.
Review
Oncology
Shawn H. R. Lee, Zhenhua Li, Si Ting Tai, Bernice L. Z. Oh, Allen E. J. Yeoh
Summary: Acute lymphoblastic leukemia (ALL) encompasses over 20 distinct genetic subtypes, each with unique clinical and prognostic characteristics. Through advances in genomic analyses, identifying these genetic subtypes allows for better risk stratification and determination of optimal treatment intensity for each patient.
Article
Genetics & Heredity
Jingying Zhang, Xiao-Jun Xu, Lixia Liu, Hua Song, Heping Shen, Weiqun Xu, Fenying Zhao, Juan Liang, Chan Liao, Yan Wang, Tian Xia, Shanbo Cao, Yongmin Tang, Jiayue Qin, Diying Shen
Summary: This study investigated the association between gene mutations and clinical features in Chinese children with B-ALL. IKZF1 mutations were found to be associated with high white blood cell count, IL7R gene mutation, low glucocorticoid sensitivity, and high minimal residual disease.
FRONTIERS IN GENETICS
(2022)
Article
Oncology
Agata Pastorczak, Anna Hogendorf, Zuzanna Urbanska, Edyta Budzynska, Dorota Jesionek-Kupnicka, Agnieszka Gach, Wanda Hawula, Robert Smigiel, Pawel Skiba, Maria Sasiadek, Monika Lejman, Maria Constatinou, Beata S. Lipska-Zietkiewicz, Wojciech Mlynarski
Summary: Microdeletions of 7p12.1 encompassing the IKZF1 gene locus are rare, with a potential link to childhood acute lymphoblastic leukemia (ALL). Among 4581 Polish individuals, two cases of 7p12.1 deletion were identified, with one individual developing ALL.
GENES CHROMOSOMES & CANCER
(2021)
Article
Oncology
Tobias M. Dantonello, Mutlu Kartal-Kaess, Christoph Aebi, Franziska Suter-Riniker, Jasmin D. Busch, Susanne Kubetzko, Jean-Pierre Bourquin, Jochen Roessler
Summary: Children with hematologic malignancies infected with COVID-19 may experience milder symptoms during infection, with a similar seroconversion period to immunocompetent adults. Despite prolonged myelosuppression, there were no secondary infections, and the treatment delay caused by the infection did not negatively impact the leukemia. Additionally, intriguingly, the residual leukemia even decreased without any antileukemic therapy.
JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY
(2021)
Article
Medicine, Research & Experimental
Rahul S. Bhansali, Malini Rammohan, Paul Lee, Anouchka P. Laurent, Qiang Wen, Praveen Suraneni, Bon Ham Yip, Yi-Chien Tsai, Silvia Jenni, Beat Bornhauser, Aurelie Siret, Corinne Fruit, Alexandra Pacheco-Benichou, Ethan Harris, Thierry Besson, Benjamin J. Thompson, Young Ah Goo, Nobuko Hijiya, Maria Vilenchik, Shai Izraeli, Jean-Pierre Bourquin, Sebastien Malinge, John D. Crispino
Summary: The study reveals that DYRK1A is overexpressed in and essential for B-ALL, with FOXO1 and STAT3 being critical substrates. Loss of DYRK1A-mediated FOXO1 and STAT3 signaling disrupts DNA damage and ROS regulation, leading to preferential cell death in leukemic B cells.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Oncology
Zeljko Antic, Jiangyan Yu, Beat C. Bornhauser, Stefan H. Lelieveld, Cedric G. van der Ham, Simon van Reijmersdal, Lionel Morgado, Sarah Elitzur, Jean-Pierre Bourquin, Giovanni Cazzaniga, Cornelia Eckert, Mireia Camos, Rosemary Sutton, Helene Cave, Anthony Moorman, Edwin Sonneveld, Ad Geurts van Kessel, Frank N. van Leeuwen, Peter M. Hoogerbrugge, Esme Waanders, Roland P. Kuiper
Summary: Early relapses in BCP-ALL often arise from minor subclones at diagnosis. Understanding the therapeutic pressure driving these events may help develop improved therapies.
PEDIATRIC BLOOD & CANCER
(2022)
Article
Hematology
Franco Locatelli, Gerhard Zugmaier, Noemi Mergen, Peter Bader, Sima Jeha, Paul-Gerhardt Schlegel, Jean-Pierre Bourquin, Rupert Handgretinger, Benoit Brethon, Claudia Roessig, William N. Kormany, Puneeth Viswagnachar, Christiane Chen-Santel
Summary: This study examined the safety and efficacy of blinatumomab in pediatric patients with relapsed/refractory B-cell precursor acute lymphoblastic leukemia (R/R B-ALL). The results showed that blinatumomab is a safe and effective treatment option for pediatric R/R B-ALL, inducing complete response (CR) and measurable residual disease (MRD) response, and improving relapse-free survival (RFS) and overall survival (OS).
Article
Hematology
Kristina Mueller, Fotini Vogiatzi, Dorothee Winterberg, Thies Rosner, Lennart Lenk, Lorenz Bastian, Carina L. Gehlert, Marie-Pauline Autenrieb, Monika Bruggemann, Gunnar Cario, Martin Schrappe, Andreas E. Kulozik, Cornelia Eckert, Anke K. Bergmann, Beat Bornhauser, Jean-Pierre Bourquin, Thomas Valerius, Matthias Peipp, Christian Kellner, Denis M. Schewe
Summary: This study suggests that combining CD47 blockade with Dara is a promising therapy for T-ALL, especially for relapsed/refractory disease harboring a dismal prognosis in patients.
Review
Oncology
Erica Brivio, Andre Baruchel, Auke Beishuizen, Jean-Pierre Bourquin, Patrick A. Brown, Todd Cooper, Lia Gore, E. Anders Kolb, Franco Locatelli, Shannon L. Maude, Francis J. Mussai, Britta Vormoor-Burger, Josef Vormoor, Arend von Stackelberg, C. Michel Zwaan
Summary: Despite improvements in treating newly diagnosed leukaemia and lymphoma in children, refractory or relapsed cases remain difficult to manage. Novel agents that offer less toxicity while maintaining efficacy are being explored. However, drug development for paediatric cancers lags behind adult therapeutic options.
EUROPEAN JOURNAL OF CANCER
(2022)
Article
Oncology
Tessa Skroblyn, Jara J. Joedicke, Madlen Pfau, Kerstin Krueger, Jean-Pierre Bourquin, Shai Izraeli, Cornelia Eckert, Uta E. Hoepken
Summary: The study identified CXCL12-CXCR4 as the leading signaling axis for B-ALL cell migration and survival in the testicular leukemic niche. CXCR4 was found to be the only chemokine receptor robustly expressed on B-ALL cells in both diagnosis and relapse samples. Blocking CXCR4 functions showed promising results in preventing testicular infiltration and overall development of leukemia.
JOURNAL OF PATHOLOGY
(2022)
Article
Oncology
Paulina Richter-Pechanska, Joachim B. Kunz, Tobias Rausch, Busra Erarslan-Uysal, Beat Bornhauser, Viktoras Frismantas, Yassen Assenov, Martin Zimmermann, Margit Happich, Caroline von Knebel-Doeberitz, Nils von Neuhoff, Rolf Kohler, Martin Stanulla, Martin Schrappe, Gunnar Cario, Gabriele Escherich, Renate Kirschner-Schwabe, Cornelia Eckert, Smadar Avigad, Stefan M. Pfister, Martina U. Muckenthaler, Jean-Pierre Bourquin, Jan O. Korbel, Andreas E. Kulozik
Summary: This study investigates the mechanisms of T-ALL relapse and reveals fundamentally different mechanisms driving type-1 and type-2 relapses. Type-1 relapses are characterized by IL7R upregulation, while type-2 relapses involve constitutional cancer predisposition gene mutations, genetic and epigenetic remodeling, and somatic hypermutator phenotypes. The study also finds that T-ALLs that later develop into type-2 relapses already have complex subclonal architecture even at the time of initial diagnosis.
Article
Oncology
Elad Jacoby, Sara Ghorashian, Britta Vormoor, Barbara De Moerloose, Nicole Bodmer, Olga Molostova, Asaf D. Yanir, Jochen Buechner, Ronit Elhasid, Bella Bielorai, Srdan Rogosic, Marie-Emilie Dourthe, Michael Maschan, Claudia Rossig, Amos Toren, Arend von Stackelberg, Franco Locatelli, Peter Bader, Martin Zimmermann, Jean Pierre Bourquin, Andre Baruchel
Summary: CAR T-cell therapy shows effectiveness in treating relapsed BCP-ALL patients with CNS involvement, but the risk of neurotoxicity and CNS relapse remains.
Article
Biochemistry & Molecular Biology
Laura Hinze, Sabine Schreek, Andre Zeug, Nurul Khalida Ibrahim, Beate Fehlhaber, Lorent Loxha, Buesra Cinar, Evgeni Ponimaskin, James Degar, Connor McGuckin, Gabriela Chiosis, Cornelia Eckert, Gunnar Cario, Beat Bornhauser, Jean-Pierre Bourquin, Martin Stanulla, Alejandro Gutierrez
Summary: The tolerance of amino acid starvation is crucial for cellular fitness. A study found that resistance to asparagine starvation depends on a low-complexity domain in GSK3 alpha, but not in its paralog GSK3 beta. This domain mediates the assembly of GSK3 alpha with components of the ubiquitin-proteasome system in response to amino acid depletion. The formation of these assemblies, known as GSK3 alpha bodies, maximizes the efficiency of proteasomal protein degradation and is associated with asparaginase resistance in leukemia.
Article
Hematology
Fotini Vogiatzi, Julia Heymann, Kristina Muller, Dorothee Winterberg, Aneta Drakul, Thies Rosner, Lennart Lenk, Michelle Heib, Carina Lynn Gehlert, Gunnar Cario, Martin Schrappe, Alexander Claviez, Beat Bornhauser, Jean-Pierre Bourquin, Simon Bomken, Dieter Adam, Fabian-Simon Frielitz, Britta Maecker-Kolhoff, Martin Stanulla, Thomas Valerius, Matthias Peipp, Christian Kellner, Denis M. Schewe
Summary: The addition of the Bcl-2 inhibitor venetoclax enhances the efficacy of therapeutic antibodies by increasing antibody-dependent cellular phagocytosis mediated by macrophages.
Article
Hematology
Sara Ghorashian, Elad Jacoby, Barbara De Moerloose, Susana Rives, Denise Bonney, Geoff Shenton, Peter Bader, Nicole Bodmer, Agueda Molinos Quintana, Blanca Herrero, Mattia Algeri, Franco Locatelli, Kim Vettenranta, Berta Gonzalez, Andishe Attarbaschi, Stephen Harris, Jean Pierre Bourquin, Andre Baruchel
Summary: This study analyzed the feasibility, efficacy, and safety of tisagenlecleucel treatment in young children and infants with acute lymphoblastic leukemia. The results suggest that tisagenlecleucel has antitumor activity and an acceptable safety profile for this age group.
LANCET HAEMATOLOGY
(2022)
Letter
Hematology
Martin Stanulla, Denis M. M. Schewe, Beat Bornhauser, Jean-Pierre Bourquin, Cornelia Eckert, Wolfgang Eberl, Saskia Wolf, Julian Wolf, Fotini Vogiatzi, Anke K. K. Bergmann, Gunnar Cario, Rita Beier, Martin Sauer, Christian P. P. Kratz, Britta Maecker-Kolhoff
ANNALS OF HEMATOLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Hyobin Jeong, Karen Grimes, Kerstin K. Rauwolf, Peter-Martin Bruch, Tobias Rausch, Patrick Hasenfeld, Eva Benito, Tobias Roider, Radhakrishnan Sabarinathan, David Porubsky, Sophie A. Herbst, Busra Erarslan-Uysal, Johann-Christoph Jann, Tobias Marschall, Daniel Nowak, Jean-Pierre Bourquin, Andreas E. Kulozik, Sascha Dietrich, Beat Bornhauser, Ashley D. Sanders, Jan O. Korbel
Summary: This study introduces a computational method called scNOVA, which utilizes Strand-seq to analyze structural variations in single cells and infer gene expression. The research reveals the impact of structural variations on gene regulation and signaling pathways, and successfully applies the method to the study of chronic lymphocytic leukemia and T cell acute lymphoblastic leukemia.
NATURE BIOTECHNOLOGY
(2023)
Article
Hematology
Malwine J. Barz, Lena Behrmann, Danaelle Capron, Gabriele Zuchtriegel, Fabio D. Steffen, Leo Kunz, Yang Zhang, Iria Jimenez Vermeerbergen, Blerim Marovca, Moritz Kirschmann, Antonia Zech, Cesar Nombela-Arrieta, Urs Ziegler, Timm Schroeder, Beat Bornhauser, Jean -Pierre Bourquin
Summary: Persistence of residual disease after induction chemotherapy is a strong predictor of relapse in acute lymphoblastic leukemia (ALL). Bone marrow microenvironment plays a role in treatment resistance. By using three-dimensional fluorescence imaging, specific sites in the bone marrow were identified where B-cell precursor ALL cells and T-ALL cells preferentially reside and interact with different components of the microenvironment. These lineage-dependent differences suggest potential targets for improving treatment.
