Review
Biochemistry & Molecular Biology
Oriol de Barrios, Maribel Parra
Summary: BCP-ALL is a highly aggressive malignancy with worse prognosis in infants. Genetic signatures and epigenetic alterations play a role in leukemogenesis, with DNA methylation patterns and histone modifications impacting oncogene activation. An integrated understanding of epigenetic disorders is crucial for improving therapeutic options and disease prognosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Ekaterina Mikhailova, Olga Illarionova, Alexander Komkov, Elena Zerkalenkova, Ilgar Mamedov, Larisa Shelikhova, Yulia Olshanskaya, Natalia Miakova, Galina Novichkova, Alexander Karachunskiy, Michael Maschan, Alexander Popov
Summary: This study aimed to develop an antibody panel and data analysis algorithm for reliable minimal residual disease (MRD) detection in B-cell precursor acute lymphoblastic leukemia (BCP-ALL) patients treated with CD19-directed therapy. The approach was adapted for possible CD19 loss and showed high qualitative concordance rates when compared to molecular techniques.
Article
Oncology
Jae Wook Lee, Yonggoo Kim, Ari Ahn, Jong Mi Lee, Jae Won Yoo, Seongkoo Kim, Bin Cho, Nack-Gyun Chung, Myungshin Kim
Summary: The study demonstrates the clinical implication of NGS-based Ig clonality assay for MRD assessment in pediatric B-ALL patients, with normalized post-induction MRD <0.01% being a significant prognostic indicator.
FRONTIERS IN ONCOLOGY
(2022)
Review
Pathology
Sindhu Cherian, Lorinda A. Soma
Summary: Assessment for minimal/measurable residual disease (MRD) in B lymphoblastic leukemia/ lymphoma (B-LL/L) using flow cytometry is becoming standard practice, providing powerful prognostic information. Understanding normal immunophenotypic patterns and the impact of therapy on these patterns is crucial for accurate evaluation.
AMERICAN JOURNAL OF CLINICAL PATHOLOGY
(2021)
Review
Oncology
Gloria Paz Contreras Yametti, Talia H. Ostrow, Sylwia Jasinski, Elizabeth A. Raetz, William L. Carroll, Nikki A. Evensen
Summary: Acute lymphoblastic leukemia minimal residual disease (MRD) is residual leukemia cells present after achieving complete remission, with significant impact on prognosis. Rapid reduction of MRD indicates leukemia sensitivity to therapy, aiding in risk stratification and treatment adjustment.
Article
Oncology
Janine Stutterheim, Inge M. van der Sluis, Paola de Lorenzo, Julia Alten, Philip Ancliffe, Andishe Attarbaschi, Benoit Brethon, Andrea Biondi, Myriam Campbell, Giovanni Cazzaniga, Gabriele Escherich, Alina Ferster, Rishi S. Kotecha, Birgitte Lausen, Chi Kong Li, Luca Lo Nigro, Franco Locatelli, Rolf Marschalek, Claus Meyer, Martin Schrappe, Jan Stary, Ajay Vora, Jan Zuna, Vincent H. J. van der Velden, Tomasz Szczepanski, Maria Grazia Valsecchi, Rob Pieters
Summary: MRD levels are predictive of outcomes in infant acute lymphoblastic leukemia, helping to guide treatment interventions.
JOURNAL OF CLINICAL ONCOLOGY
(2021)
Article
Oncology
Mingfeng Zhang, Tong Qi, Lu Yang, Daniel Kolarich, Nora Heisterkamp
Summary: This study demonstrates that the expression levels of ST6Gal1 in BCP-ALL cells can affect cell survival and sensitivity to chemotherapy, indicating an important role of ST6Gal1 in B-cell development and tumorigenesis.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Emma Kroeze, Laura Arias Padilla, Max Bakker, Judith M. Boer, Melanie M. Hagleitner, Birgit Burkhardt, Takeshi Mori, Andishe Attarbaschi, Jaime Verdu-Amoros, Marta Pillon, Liliya Anderzhanova, Edita Kabickova, Alan K. S. Chiang, Rejin Kebudi, Karin Mellgren, Jelena Lazic, Janez Jazbec, Jules P. P. Meijerink, Auke Beishuizen, Jan L. C. Loeffen
Summary: B-cell lymphoblastic lymphoma (BCP-LBL) and B-cell acute lymphoblastic leukemia (BCP-ALL) are both malignancies of immature B-cells. BCP-ALL is the most common hematological malignancy in childhood, while BCP-LBL accounts for only 1% of all hematological malignancies in children. Therefore, BCP-ALL has been well studied and treatment protocols have changed over the last decades, whereas treatment for BCP-LBL has stayed roughly the same.
Article
Oncology
Chih-Hsiang Yu, Shiann-Tarng Jou, Ying-Hui Su, Elane Coustan-Smith, Gang Wu, Chao-Neng Cheng, Meng-Yao Lu, Kai-Hsin Lin, Kang-Hsi Wu, Shu-Huey Chen, Fang-Liang Huang, Hsiu-Hao Chang, Jinn-Li Wang, Hsiu-Ju Yen, Meng-Ju Li, Shu-Wei Chou, Wan-Ling Ho, Yen-Lin Liu, Chia-Ching Chang, Ze-Shiang Lin, Chien-Yu Lin, Hsuan-Yu Chen, Yu-Ling Ni, Dong-Tsamn Lin, Shu-Wha Lin, Jun J. Yang, Yen-Hsuan Ni, Ching-Hon Pui, Sung-Liang Yu, Yung-Li Yang
Summary: This study analyzed data from two consecutive protocols to determine the clinical impact of minimal/measurable residual disease (MRD) and tumor genetic subtypes in newly diagnosed pediatric acute lymphoblastic leukemia (ALL) patients. The results showed that MRD-directed therapy improved outcomes for pediatric ALL, especially for standard-risk patients. This study provides important data to inform the design of future clinical trials in Taiwan.
Article
Cell Biology
Albert Manzano-Munoz, Clara Alcon, Pablo Menendez, Manuel Ramirez, Felix Seyfried, Klaus-Michael Debatin, Luder H. Meyer, Josep Samitier, Joan Montero
Summary: Multiple targeted therapies are being explored for improving clinical outcome in pediatric and young adult BCP-ALL, especially for relapsed patients. Using DBP evaluation, MEK inhibitor trametinib and multi-target tyrosine kinase inhibitor sunitinib were found to enhance apoptotic priming in NRAS-mutant and KMT2A-rearranged cell lines with high FLT3 expression, respectively.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Hematology
Yu-juan Xue, Yu Wang, Yue-ping Jia, Ying-xi Zuo, Jun Wu, Ai-dong Lu, Le-ping Zhang
Summary: Acute lymphoblastic leukemia (ALL) is a heterogeneous disease with prognostic factors including minimal residual disease (MRD) and cytogenetic abnormalities. The outcomes of treatment based on MRD monitoring varied between distinct leukemia subtypes, highlighting the importance of MRD-guided therapy. Sequential MRD measurement is crucial for refined risk stratification and identifying adverse prognostic indicators.
INTERNATIONAL JOURNAL OF HEMATOLOGY
(2021)
Article
Oncology
Huirong Mai, Qin Li, Guobing Wang, Ying Wang, Shilin Liu, Xue Tang, Fen Chen, Guichi Zhou, Yi Liu, Tonghui Li, Lulu Wang, Chunyan Wang, Feiqiu Wen, Sixi Liu
Summary: This study explored the feasibility of using Next-generation sequencing (NGS) technology to detect minimal residual disease (MRD) in childhood acute lymphoblastic leukemia (ALL). The results showed that NGS is more sensitive than multiparametric flow cytometry (MFC) and real-time quantitative PCR (RQ-PCR) in detecting MRD. Furthermore, the number of clonal rearrangement sequences detected by NGS before treatment is an independent factor in predicting whether MRD can become negative after chemotherapy.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2023)
Article
Medicine, Research & Experimental
Tiago Oliveira, Mingfeng Zhang, Eun Ji Joo, Hisham Abdel-Azim, Chun-Wei Chen, Lu Yang, Chih-Hsing Chou, Xi Qin, Jianjun Chen, Kathirvel Alagesan, Andreia Almeida, Francis Jacob, Nicolle H. Packer, Mark von Itzstein, Nora Heisterkamp, Daniel Kolarich
Summary: This study integrated transcriptomics, proteomics and glycomics data to reveal extensive remodeling of glycocalyx in MLL-r cells, identifying potential therapeutic targets and previously unknown protein targets. The research demonstrated the importance of a systematic combined multi-omics approach in providing important diagnostic information that may be missed with a single omics technology.
Article
Oncology
Shu-Wei Chou, Ying-Hui Su, Meng-Yao Lu, Hsiu-Hao Chang, Yung-Li Yang, Dong-Tsamn Lin, Kai-Hsin Lin, Elaine Coustan-Smith, Shiann-Tarng Jou
Summary: This study aimed to find an effective way to monitor minimal residual disease (MRD) in patients with acute lymphoblastic leukemia (ALL) using flow cytometry. The study found that the combination of Hsp27 with CD73, CD58, CD24, and backbone markers can detect MRD in virtually all ALL patients.
PEDIATRIC BLOOD & CANCER
(2023)
Article
Medical Laboratory Technology
Kevin E. Shopsowitz, Lorraine Liu, Audi Setiadi, Maryam Al-Bakri, Suzanne Vercauteren
Summary: In this study, optimized radar plots were developed for B-ALL MRD analysis, which successfully distinguished diverse B-lymphoblast populations and non-malignant CD19-positive populations. The optimized radar plots outperformed PCA plots and showed comparable performance to UMAP, with better generalizability to new data. This novel optimization strategy for radar plots could be applied to other MRD panels and clinical scenarios.
CYTOMETRY PART B-CLINICAL CYTOMETRY
(2022)
Article
Oncology
Kim Klein, H. Berna Beverloo, Martin Zimmermann, Susana C. Raimondi, Christine von Neuhoff, Valerie Haas, Romy van Weelderen, Jacqueline Cloos, Jonas Abrahamsson, Yves Bertrand, Michael Dworzak, Alcira Fynn, Brenda Gibson, Shau-Yin Ha, Christine J. Harrison, Henrik Hasle, Sarah Elitzur, Guy Leverger, Alexei Maschan, Bassem Razzouk, Dirk Reinhardt, Carmelo Rizzari, Pter Smisek, Ursula Creutzig, Gertjan J. L. Kaspers
Summary: Cytogenetic profiles and karyotypic changes at relapse play a significant role in predicting survival outcomes for children with relapsed AML, with certain abnormalities associated with better or worse prognosis. Early treatment response, time to relapse, and cytogenetic profile at relapse are important prognostic factors, outweighing karyotypic instability per se.
PEDIATRIC BLOOD & CANCER
(2022)
Article
Biology
Matthias Woedlinger, Michael Reiter, Lisa Weijler, Margarita Maurer-Granofszky, Angela Schumich, Elisa O. Sajaroff, Stefanie Groeneveld-Krentz, Jorge G. Rossi, Leonid Karawajew, Richard Ratei, Michael N. Dworzak
Summary: This study presents an automated method to compute the Minimal Residual Disease (MRD) value directly from FCM data in Acute Lymphoblastic Leukemia (ALL) patients. The method utilizes a neural network based on the transformer architecture to identify blast cells in samples. Evaluation on multiple datasets shows that the proposed method outperforms existing methods.
COMPUTERS IN BIOLOGY AND MEDICINE
(2022)
Article
Pathology
Elena Kipf, Franziska Schlenker, Nadine Borst, Marion Fillies, Renate Kirschner-Schwabe, Roland Zengerle, Cornelia Eckert, Felix von Stetten, Michael Lehnert
Summary: The authors developed personalized multiplex mediator probe PCR (MP PCR) for MRD monitoring in ALL, which can accurately quantify more MRD markers in less sample material. This helps reduce the impact of clonal tumor evolution on clinical outcomes. Additionally, they increased the multiplex level to 4-plex and met the EuroMRD requirements for reliable quantification, facilitating and accelerating MP PCR assay development for standardized personalized diagnostics.
JOURNAL OF MOLECULAR DIAGNOSTICS
(2022)
Article
Pathology
Claudia Schwinghammer, Johannes Koopmann, Guranda Chitadze, Leonid Karawajew, Monika Brueggemann, Cornelia Eckert
Summary: This study compares the performance of real-time quantitative PCR (qPCR) and droplet digital PCR (ddPCR) in minimal residual disease (MRD) monitoring for acute lymphoblastic leukemia (ALL). The results demonstrate that ddPCR outperforms qPCR in terms of quantitative limit of detection and sensitivity. Additionally, the concordance of quantitative values between ddPCR and Flow is higher than that between ddPCR and qPCR.
JOURNAL OF MOLECULAR DIAGNOSTICS
(2022)
Article
Oncology
Anna Gidl, Anna Fuereder, Martin Benesch, Michael Dworzak, Gernot Engstler, Neil Jones, Gabriele Kropshofer, Ulrike Poetschger, Fiona Poyer, Melanie Tamesberger, Volker Witt, Georg Mann, Andishe Attarbaschi
Summary: Venous thromboembolism (VTE) is a common and serious complication in the treatment of pediatric acute lymphoblastic leukemia (ALL). This study analyzed 1026 ALL patients aged 1-18 years and identified the incidence and risk factors of VTE. The results showed that VTE was most commonly observed during induction and early consolidation therapy, and older age was the main patient-related risk factor.
PEDIATRIC HEMATOLOGY AND ONCOLOGY
(2023)
Article
Oncology
Elen Oliveira, Elaine S. Costa, Juana Ciudad, Giuseppe Gaipa, Lukasz Sedek, Susana Barrena, Tomasz Szczepanski, Chiara Buracchi, Daniela Silvestri, Patricia F. R. Siqueira, Fabiana Mello, Rafael C. Torres, Leonardo M. R. Oliveira, Isabelle V. C. Fay-Neves, Edwin Sonneveld, Vincent H. J. van der Velden, Esther Mejstrikova, Josep-Maria Ribera, Valentino Conter, Martin Schrappe, Jacques J. M. van Dongen, Marcelo G. P. Land, Alberto Orfao
Summary: An imbalanced ratio of endothelial cells (EC) to mesenchymal stem cells (MSC) in the bone marrow at day +78 of therapy is associated with a shorter disease-free survival (DFS) in B-cell precursor acute lymphoblastic leukemia (BCP-ALL) patients, independent of their measurable residual disease (MRD) status.
Meeting Abstract
Hematology
Federico Lussana, Chiara Francesca Magnani, Giuseppe Gaipa, Stefania Galimberti, Giuseppe Gritti, Daniela Belotti, Sara Napolitano, Chiara Buracchi, Gian Maria Borleri, Benedetta Rambaldi, Giuliana Rizzuto, Anna Grassi, Muriel Paganessi, Silvia Ferrari, Sarah Tettamanti, Giovanni Gazzaniga, Chiara Capelli, Elisa Gotti, Martino Introna, Adriana Balduzzi, Maria Grazia Valsecchi, Giuseppe Dastoli, Alessandro Rambaldi, Andrea Biondi
Meeting Abstract
Hematology
Benedetta Rambaldi, Stefania Galimberti, Giuliana Rizzuto, Chiara Francesca Magnani, Chiara Buracchi, Giulia Risca, Martina Paredi, Daniela Belotti, Alex Moretti, Marianna Ponzo, Sarah Tettamanti, Gian Maria Borleri, Cristian Meli, Muriel Paganessi, Silvia Zaninelli, Elisa Gotti, Chiara Capelli, Martino Introna, Federico Lussana, Giuseppe Gritti, Silvia Ferrari, Anna Grassi, Sara Napolitano, Adriana Balduzzi, Maria Grazia Valsecchi, Giuseppe Dastoli, Alessandro Rambaldi, Andrea Biondi, Giuseppe Gaipa
Article
Biochemistry & Molecular Biology
Angela Genchi, Elena Brambilla, Francesca Sangalli, Marta Radaelli, Marco Bacigaluppi, Roberto Furlan, Annapaola Andolfo, Denise Drago, Cinzia Magagnotti, Giulia Maria Scotti, Raffaella Greco, Paolo Vezzulli, Linda Ottoboni, Marco Bonopane, Daniela Capilupo, Francesca Ruffini, Daniela Belotti, Benedetta Cabiati, Stefania Cesana, Giada Matera, Letizia Leocani, Vittorio Martinelli, Lucia Moiola, Luca Vago, Paola Panina-Bordignon, Andrea Falini, Fabio Ciceri, Anna Uglietti, Maria Pia Sormani, Giancarlo Comi, Mario Alberto Battaglia, Maria A. A. Rocca, Loredana Storelli, Elisabetta Pagani, Giuseppe Gaipa, Gianvito Martino
Summary: This study conducted a phase 1 clinical trial evaluating the feasibility, safety and tolerability of intrathecally transplanted human fetal neural precursor cells (hfNPCs) in patients with progressive multiple sclerosis (PMS). The results demonstrated that hfNPC therapy is feasible, safe and tolerable in PMS patients.
Article
Genetics & Heredity
Lorenza Bacci, Valentina Indio, Guglielmo Rambaldelli, Cristina Bugarin, Franco Magliocchetti, Alberto Del Rio, Daniela Pollutri, Fraia Melchionda, Andrea Pession, Marina Lanciotti, Carlo Dufour, Giuseppe Gaipa, Lorenzo Montanaro, Marianna Penzo
Summary: T-cell acute lymphoblastic leukemia (T-ALL) is a subtype of ALL with various genetic lesions, including mutations in genes encoding for ribosomal proteins (RPs). This study found that mutations in RPs tend to cluster together in different patients with T-ALL, suggesting that their co-occurrence may confer an advantage to leukemia cells. Additionally, a novel mutation in the RPL10 gene associated with a defect in protein synthesis was identified. These findings indicate the importance of considering genetic alterations involving ribosome biogenesis and translational control in precision medicine for T-ALL.
FRONTIERS IN GENETICS
(2022)
Article
Oncology
Anna Guarini, Giulia Radice, Nadia Peragine, Chiara Buracchi, Maria Stefania De Propris, Alice Di Rocco, Arianna Di Rocco, Sabina Chiaretti, Alex Moretti, Sara Napolitano, Maurizio Martelli, Adriana Balduzzi, Giuseppe Gaipa, Andrea Biondi, Robin Foa
Summary: This study investigated the effects of tisagenlecleucel administration on immune populations in patients with R/R DLBCL and B-ALL. The results showed that tisagenlecleucel was able to control the disease and induce a marked modulation of the immune system, with increased CD3(+), CD4(+), CD8(+), NK cells and decreased Treg cells, as well as increased IFN? and TNFa production by T lymphocytes.
Proceedings Paper
Computer Science, Artificial Intelligence
Florian Kowarsch, Lisa Weijler, Matthias Woedlinger, Michael Reiter, Margarita Maurer-Granofszky, Angela Schumich, Elisa O. Sajaroff, Stefanie Groeneveld-Krentz, Jorge G. Rossi, Leonid Karawajew, Richard Ratei, Michael N. Dworzak
Summary: This study proposes a Transformer-based approach that mimics the decision process of medical experts to classify cells in Flow Cytometry (FCM) data. The model achieves state-of-the-art performance for automated blast cell identification in leukemia therapy, while providing transparent results and explainable visualizations for human experts.
INTERPRETABILITY OF MACHINE INTELLIGENCE IN MEDICAL IMAGE COMPUTING, IMIMIC 2022
(2022)
Article
Hematology
Fiona Poyer, Anna Fuereder, Wolfgang Holter, Christina Peters, Heidrun Boztug, Michael Dworzak, Gernot Engstler, Waltraud Friesenbichler, Stefan Koehrer, Roswitha Lueftinger, Leila Ronceray, Volker Witt, Herbert Pichler, Andishe Attarbaschi
Summary: This article emphasizes the challenges faced by pediatric acute lymphoblastic leukemia (ALL) patients who experience systemic relapse after their first hematopoietic stem cell transplantation (HSCT). Individualized treatment strategies integrating conventional chemotherapy, immunotherapeutic approaches, and second allogeneic HSCT need to be developed.
THERAPEUTIC ADVANCES IN HEMATOLOGY
(2022)
Correction
Hematology
Beat Bornhauser, Gunnar Cario, Anna Rinaldi, Thomas Risch, Virginia Rodriguez Martinez, Moritz Schuette, Hans-Joerg Warnatz, Nastassja Scheidegger, Paulina Mirkowska, Martina Temperli, Claudia Moller, Angela Schumich, Michael Dworzak, Andishe Attarbaschi, Monika Brueggemann, Mathias Ritgen, Ester Mejstrikova, Andreas Hofmann, Barbara Buldini, Pamela Scarparo, Giuseppe Basso, Oscar Maglia, Giuseppe Gaipa, Tessa Lara Skroblyn, Quy A. Ngo, Geertruij te Kronnie, Elena Vendramini, Renate Panzer-Gruemayer, Malwine Jeanette Barz, Blerim Marovca, Mathias Hauri-Hohl, Felix Niggli, Cornelia Eckert, Martin Schrappe, Martin Stanulla, Martin Zimmermann, Bernd Wollscheid, Marie-Laure Yaspo, Jean-Pierre Bourquin