Article
Genetics & Heredity
Atsushi Watanabe, Kunio Miyake, Koshi Akahane, Kumiko Goi, Keiko Kagami, Hideo Yagita, Takeshi Inukai
Summary: Immunotherapies specific for BCP-ALL, such as anti-CD19 CAR T-cells and blinatumomab, have significantly improved outcomes in refractory cases. The methylation status of DR4 and DR5 genes is associated with gene expression levels, cell-surface expression, and TRAIL-sensitivities, suggesting potential clinical relevance in predicting immunotherapy efficacy. Evaluating methylation status of DR4 and DR5 genes may be informative in certain cases with unfavorable karyotypes.
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
Biochemistry & Molecular Biology
Elena Zerkalenkova, Svetlana Lebedeva, Aleksandra Borkovskaia, Olga Soldatkina, Olga Plekhanova, Grigory Tsaur, Michael Maschan, Aleksey Maschan, Galina Novichkova, Yulia Olshanskaya
Summary: Chromosomal rearrangements of the human KMT2A/MLL gene play a significant role in acute leukemias, and can be effectively detected by next-generation sequencing. However, thorough prescreening by cytogenetics is required before conducting NGS.
Review
Oncology
Karolina Joanna Zietara, Jan Lejman, Katarzyna Wojciechowska, Monika Lejman
Summary: B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is a common hematological malignancy in children. The disease is caused by the uncontrolled proliferation of precursor cells in the bone marrow. Molecules such as microRNA (miRNA) play a role in the development of BCP-ALL. miRNA is a short non-coding RNA that regulates gene expression. It affects both pre- and post-translational processes. The stability of miRNA and its presence in circulation are useful for diagnosis and prognosis of pediatric leukemias. miRNA is gaining attention for its biomarker potential and easy detection.
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
Medicine, General & Internal
Jan Kulis, Lukasz Wawrowski, Lukasz Sedek, Lukasz Wrobel, Lukasz Slota, Vincent H. J. van der Velden, Tomasz Szczepanski, Marek Sikora
Summary: Flow cytometry technique is a diagnostic tool for B-cell precursor acute lymphoblastic leukemia, which can reveal genetic aberrations through analyzing antigen expression patterns. Machine learning methods can be used for efficient detection based on multiple markers.
JOURNAL OF CLINICAL MEDICINE
(2022)
Review
Immunology
Thomas R. Jackson, Rebecca E. Ling, Anindita Roy
Summary: Human B-lymphopoiesis is a dynamic life-long process that starts in utero and continues to change throughout postnatal life. Understanding fetal B-lymphopoiesis is crucial for comprehending normal B-lymphoid development and its relevance to disease, particularly in childhood leukemia.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Pharmacology & Pharmacy
Jesus Alonso Gandara-Mireles, Ismael Lares-Asseff, Elio Aaron Reyes Espinoza, Javier G. Blanco, Isaias Chairez Hernandez, Lourdes Patricia Cordova Hurtado, Veronica Loera Castaneda, Leslie Patron Romero, Cristina Venzor Sanchez, Hugo Payan Gandara, Dinora Arechiga Gurrola, Horacio Almanza Reyes
Summary: This study identified an evident impact of the NCF4 rs1883112 and CBR3 rs1056892 polymorphisms in increasing the risk of susceptibility to ALL. Additionally, the protective effect of the CBR3 rs1056892 gene variation against ALL was evaluated using a codominant inheritance model.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Pathology
Matthew M. Klairmont, Yinmei Zhou, Cheng Cheng, Ching-Hon Pui, Sima Jeha, Tanja A. Gruber, Yiwei Liu, Hiroto Inaba, John Kim Choi
Summary: TdT-negative B-ALL, compared to TdT-positive B-ALL, is associated with younger age, higher white blood cell count, absence of hyperdiploidy, more frequent KMT2A rearrangements, and inferior 5-year event-free survival rate. In KMT2A-rearranged B-ALL, TdT negativity is significantly associated with the MLLT1 rearrangement partner, suggesting that the high-risk features of TdT-negative B-ALL are secondary to underlying KMT2A rearrangements. Furthermore, TdT negativity is more sensitive than neuron-glial antigen 2 (NG.2) expression in detecting KMT2A rearrangements in pediatric B-ALL cases, highlighting the importance of immunophenotypic features in identifying high-risk genetic abnormalities.
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.
Review
Medicine, General & Internal
Beata Sienkiewicz-Oleszkiewicz, Malgorzata Salamonowicz-Bodzioch, Justyna Slonka, Krzysztof Kalwak
Summary: The interaction between antifungal drugs and common drugs is an important issue in pediatric hemato-oncology. This review focuses on the interaction between antifungal agents and treatment drugs for acute lymphoblastic leukemia, and found that liposomal amphotericin B has a favorable safety profile.
JOURNAL OF CLINICAL MEDICINE
(2023)
Review
Biochemistry & Molecular Biology
Kinga Panuciak, Emilia Nowicka, Angelika Mastalerczyk, Joanna Zawitkowska, Maciej Niedzwiecki, Monika Lejman
Summary: Recent years have seen significant progress in the treatment of B-cell acute lymphoblastic leukemia (ALL), with improved conventional therapy schemes and the development of new treatment forms. The 5-year survival rates now exceed 90% in pediatric patients. However, at the molecular level, there are still many variations that need to be analyzed in more detail, including aneuploidy, which is among the most common genetic changes in B-cell ALL. Our work will focus on summarizing the current state of knowledge on aneuploidy and its correlates with the treatment of B-cell ALL patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Genetics & Heredity
Tahir Mohiuddin Malla, Zafar Amin Shah, Aashiq Hussain Bhat, Manzoor Ahmad Malik, Rafia Anjum Baba, Roohi Rasool, Javaid Rasool, Sozi Ashaq, Faizanul Haq
Summary: This study aimed to investigate the incidence of ETV6/RUNX1 fusion and MLL gene rearrangement in pediatric acute lymphocytic leukemia in the Kashmir region. The results showed that the incidence of ETV6/RUNX1 fusion was 28.07% and the incidence of MLL gene rearrangement was 3.5%. These findings suggest a higher frequency of ETV6/RUNX1 fusion in pediatric ALL cases in Kashmir compared to other parts of India, and the identification of a unique chromosomal abnormality not previously reported.
Article
Oncology
Jing Feng, Ye Guo, Wenyu Yang, Yao Zou, Li Zhang, Yumei Chen, Yingchi Zhang, Xiaofan Zhu
Summary: CDKN2A/B deletions are associated with distinct characteristics in pediatric ALL, and serve as a poor prognostic factor, especially in carriers of TP53 deletions.
FRONTIERS IN ONCOLOGY
(2022)
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
Anthony Moorman, Ellie Butler, Emilio Barretta, Amy A. Kirkwood, Claire Schwab, Thomas Creasey, Daniel A. Leongamornlert, Elli Papaemmanuil, Pip Patrick, Laura Clifton-Hadley, Bela Patel, Tobias F. Menne, Andrew K. McMillan, Christine J. Harrison, Clare J. Rowntree, David Marks, Adele K. Fielding, Eleanor J. Ward, Katie Twentyman, Amir Enshaei
Summary: Chromosomal abnormalities have a significant prognostic impact on patients with B-cell precursor ALL, with specific abnormalities like KMT2A-AFF1, complex karyotype, and low hypodiploidy/near-triploidy associated with poor outcomes. Patients with BCR-ABL1 have similar outcomes to others, while JAK-STAT abnormalities are linked to a high relapse rate of 56%.
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
Jasmeet Sidhu, Ashish Narayan Masurekar, Manash Pratim Gogoi, Caroline Fong, Tasos Ioannou, Taha Lodhi, Catriona Parker, Jizhong Liu, Amy A. Kirkwood, Anthony Moorman, Kiranmoy Das, Nicholas J. Goulden, Ajay Vora, Vaskar Saha, Shekhar Krishnan
Summary: In successive UK clinical trials, polyethylene glycol-conjugated E. coli L-asparaginase was used in pediatric acute lymphoblastic leukemia patients. The treatment showed low toxicity but had wide interpatient variability. Therapeutic drug monitoring with individualized dosing could potentially optimize the treatment.
BRITISH JOURNAL OF HAEMATOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Daniel Rico, Daniel Kent, Nefeli Karataraki, Aneta Mikulasova, Rolando Berlinguer-Palmini, Brian A. Walker, Biola M. Javierre, Lisa J. Russell, Chris A. Brackley
Summary: This study used a predictive model to predict chromatin conformation of the proto-oncogene CCND1 in both healthy and malignant B cells, and found that genomic rearrangements involving CCND1 can lead to chromatin remodeling and oncogene activation.
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
Oncology
Richard Gallon, Rachel Phelps, Leigh Betts, Christine Hayes, Dino Masic, Julie A. E. Irving, Ciaron McAnulty, Vaskar Saha, Ajay Vora, Katharina Wimmer, Jayashree Motwani, Christine Macartney, John Burn, Michael S. Jackson, Anthony Moorman, Mauro Santibanez-Koref
LEUKEMIA & LYMPHOMA
(2023)
Meeting Abstract
Hematology
Jesus Gutierrez-Abril, Daniel Leongamornlert, Neerav N. Shukla, Maria Luisa Sulis, Yangyu Zhou, Max F. Levine, Emilio Barretta, SooWah Lee, Juan E. Arango-Ossa, Gunes Gundem, Juan S. Medina-Martinez, Bela Patel Wrench, Anthony Moorman, Adele K. Fielding, Andrew L. Kung, Elli Papaemmanuil
Meeting Abstract
Hematology
Amir Enshaei, Javier Martinez Martinez Elicegui, Esther Anguiano, Jude Gibson, Mirella Ampatzidou, Michael Doubek, Adele K. Fielding, Edoardo La Sala, Elizabeth Middleton, Anita W. Rijneveld, Amin T. Turki, Ajay Vora, Martin Zimmermann, Anthony Moorman
Meeting Abstract
Hematology
Bela Patel Wrench, Amy A. Kirkwood, Krisztina Zuborne Alapi, Laura Clifton-Hadley, SooWah Lee, David Marks, Anthony Moorman, Nicholas J. Morley, Pip Patrick, Zaynab Rana, Clare J. Rowntree, John A. Snowden, Adele K. Fielding
Meeting Abstract
Hematology
Hayden L. Bell, Mankaran Singh, Helen J. Blair, Olaf Heidenreich, Frederik W. van Delft, Anthony Moorman, John Lunec, Julie Irving
Meeting Abstract
Hematology
Angus Hodder, Avijeet K. Mishra, Katherine Clesham, Susan Baird, Kaljit Bhuller, Ismail Bisho, Denise Bonney, Anna Castleton, Michelle Cummins, Emmy Dickens, Lindsay George, Sara Ghorashian, Brenda Gibson, Chris Hasley, Nicholas Heaney, Rachael E. Hough, Danielle Ingham, Galina Jigoulina, Katherine Lindsay, Donna Lancaster, Majid Madni, Andrea Malone, Bethany Mitchell, Anthony Moorman, John Moppett, Vanessa McLelland, Jayashree Motwani, Emma Nicholson, Caroline Osborne, Katharine Patrick, Lamia Samrin, Sanjay Tewari, Indu Rakesh Thakur, Sujith Samarasinghe, Ajay Vora, David O'Connor
Meeting Abstract
Hematology
Daniel Leongamornlert, Jesus Gutierrez-Abril, SooWah Lee, Emilio Barretta, Thomas Creasey, Krisztina Zuborne Alapi, Max F. Levine, Juan E. Arango-Ossa, Juan S. Medina-Martinez, Amy A. Kirkwood, Laura Clifton-Hadley, Pip Patrick, David Jones, Adam P. Butler, Christine J. Harrison, Peter J. Campbell, Bela Patel Wrench, Anthony Moorman, Adele K. Fielding, Elli Papaemmanuil
Meeting Abstract
Hematology
Anna Ostergaard, Amir Enshaei, Rob Pieters, Ajay Vora, Martin A. Horstmann, Gabriele Escherich, Bertil Johansson, Mats Heyman, Kjeld Schmiegelow, Peter M. Hoogerbrugge, Monique L. den Boer, Roland P. Kuiper, Anthony Moorman, Judith M. Boer, Frank N. van Leeuwen
Article
Hematology
Anna ostergaard, Amir Enshaei, Rob Pieters, Ajay Vora, Martin A. Horstmann, Gabriele Escherich, Bertil Johansson, Mats Heyman, Kjeld Schmiegelow, Peter M. Hoogerbrugge, Monique L. den Boer, Roland P. Kuiper, Anthony V. Moorman, Judith M. Boer, Frank N. van Leeuwen
Summary: IKZF1 deletions have a significant negative impact on the survival of patients with ETV6::RUNX1 and high hyperdiploid ALL. The presence of IKZF1 deletions is associated with lower event-free survival rates, higher minimal residual disease values, and higher relapse rates in both ETV6::RUNX1 and high hyperdiploid ALL. Stratifying patients by minimal residual disease may not be sufficient for predicting outcomes in high hyperdiploid ALL, suggesting the need for additional risk stratification.
Article
Hematology
David Marks, Laura Clifton-Hadley, Mhairi Copland, Jiaull Hussain, Tobias F. Menne, Andrew McMillan, Anthony Moorman, Nicholas Morley, Dina Okasha, Bela Patel, Pip Patrick, Michael N. Potter, Clare J. Rowntree, Amy A. Kirkwood, Adele K. Fielding
Summary: This study evaluated the activity and safety of reduced-intensity conditioned allogeneic haematopoietic stem-cell transplantation (HSCT) in patients older than 40 years with acute lymphoblastic leukaemia. The results showed that this transplantation method provided good disease control with moderate graft-versus-host disease (GVHD) and achieved better-than-expected event-free survival and overall survival in this high-risk population.
LANCET HAEMATOLOGY
(2022)