Review
Oncology
Koichi Takahashi, Tomoyuki Tanaka
Summary: Myeloid malignancies, including acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), and myeloproliferative neoplasms (MPNs), are hematopoietic disorders characterized by genetic and epigenetic changes in hematopoietic stem and progenitor cells (HSPCs). Recent advancements in clonal hematopoiesis research and single cell technologies have provided new insights into the developmental process of myeloid malignancies. This review explores the intricacies of clonal evolution in myeloid malignancies and its implications for the development of new diagnostic and therapeutic approaches.
Review
Biochemistry & Molecular Biology
Diana Karen Mendiola-Soto, Diego Alberto Barcenas-Lopez, Carlos Jhovani Perez-Amado, Gabriela Marisol Cruz-Miranda, Juan Manuel Mejia-Arangure, Julian Ramirez-Bello, Alfredo Hidalgo-Miranda, Silvia Jimenez-Morales
Summary: Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer, and although cure rates have increased, a significant number of patients still relapse. The role of microRNAs (miRNAs) as non-coding RNA genes in ALL has gained interest in terms of understanding the disease's molecular mechanisms and identifying clinical biomarkers. Consistent findings suggest that miRNAs can be useful in distinguishing between different types of leukemia and predicting chemotherapy response. However, there is limited research on the molecular interplay between miRNAs and their targeted genes. This review aims to discuss the various ways miRNAs could be involved in ALL and their clinical implications.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Hematology
Haley J. Abel, Karolyn A. Oetjen, Christopher A. Miller, Sai M. Ramakrishnan, Ryan B. Day, Nichole M. Helton, Catrina C. Fronick, Robert S. Fulton, Sharon E. Heath, Stefan P. Tarnawsky, Sridhar Nonavinkere Srivatsan, Eric J. Duncavage, Molly C. Schroeder, Jacqueline E. Payton, David H. Spencer, Matthew J. Walter, Peter Westervelt, John F. Dipersio, Timothy J. Ley, Daniel C. Link
Summary: TP53-mutated myeloid malignancies are associated with complex cytogenetics and extensive structural variants. The specific chromosome abnormalities are distinct to each cancer type, suggesting a dependence on the tissue of origin. NF1 and ETV6 mutations are highly enriched in TP53-mutated AML, and abnormal telomeric sequences were detected in the interstitial regions of chromosomes.
Review
Immunology
Jo Caers, Elodie Duray, Louise Vrancken, Guillaume Marcion, Valentina Bocuzzi, Kim De Veirman, Ahmet Krasniqi, Margaux Lejeune, Nadia Withofs, Nick Devoogdt, Mireille Dumoulin, Amelie Eriksson Karlstrom, Matthias D'Huyvetter
Summary: This review discusses the different strategies introduced for the noninvasive detection and treatment of hematological malignancies by radiotheranostic agents, and explores the future applications of these agents.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Cell Biology
Elena De Marchi, Anna Pegoraro, Elena Adinolfi
Summary: The P2X7 receptor, known for its role in immune responses, has emerged as a critical factor in promoting cancer. Studies have shown a correlation between P2X7 alterations and lymphoproliferative and myeloproliferative diseases. Recent research suggests that P2X7 and its genetic variants could be new biomarkers in hematological malignancies, and that both P2X7 antagonists and agonists could be potential therapeutic tools.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Oncology
Ajay Abraham, William Matsui
Summary: Myeloid malignancies arise from normal hematopoiesis and the Hedgehog (HH) signaling pathway plays an important role in these diseases, with SMO inhibitors approved for the treatment of acute myeloid leukemia (AML). Despite the broad activity of SMO inhibitors in AML, clinical studies in other myeloid malignancies remain inconclusive and further research is needed to explore their efficacy.
Review
Oncology
Olga Garcia Ruiz, Jose Manuel Sanchez-Maldonado, Miguel Angel Lopez-Nevot, Paloma Garcia, Angelica Macauda, Francisca Hernandez-Mohedo, Pedro Antonio Gonzalez-Sierra, Manuel Martinez-Bueno, Eva Perez, Fernando Jesus Reyes-Zurita, Daniele Campa, Federico Canzian, Manuel Jurado, Juan Jose Rodriguez-Sevilla, Juan Sainz
Summary: Autophagy plays a dual role in cancer, both promoting cancer cell survival and preventing tumor growth and progression. It is important in hematological malignancies and may serve as a potential therapeutic target. Genetic variants within autophagy-related genes may modulate the risk of developing hemopathies and patient survival.
Review
Chemistry, Multidisciplinary
Wenxing Gu, Ruobing Qu, Fenghua Meng, Jeroen J. L. M. Cornelissen, Zhiyuan Zhong
Summary: Hematological malignancies are difficult to treat with traditional methods due to drug resistance, but new polymeric nanomedicines show promise in overcoming these challenges and improving therapeutic outcomes.
JOURNAL OF CONTROLLED RELEASE
(2021)
Review
Cell Biology
Debora Bifano Pimenta, Vanessa Araujo Varela, Tarcila Santos Datoguia, Victoria Bulcao Caraciolo, Gabriel Herculano Lopes, Welbert Oliveira Pereira
Summary: Bone marrow is a complex tissue that regulates hematopoiesis, with AML developing in this microenvironment. Cells and molecules within the hematopoietic niche interact to influence leukemia development, suggesting that targeting the bone marrow microenvironment could be a promising strategy for AML treatment.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Binsah George, Hagop Kantarjian, Natalia Baran, Joseph Douglas Krocker, Adan Rios
Summary: Mutations in the tumor suppressor gene TP53 are strongly linked to poor survival outcomes in AML patients, particularly in cases with complex cytogenetics or therapy-related AML. Despite the prevalence of TP53 mutations in cancer, targeted therapeutic interventions for these mutations remain limited, highlighting the need for personalized treatment strategies. Understanding the functional differences of p53 mutants is crucial in developing effective therapies for AML patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Brooks A. Benard, Logan B. Leak, Armon Azizi, Daniel Thomas, Andrew J. Gentles, Ravindra Majeti
Summary: This study aggregates multiple AML cohorts to explore the correlation between clonal abundance of somatic mutations and clinical outcomes. High variant allele frequency for certain mutations is associated with poor prognosis, while increased GATA2 variant allele frequency correlates with better outcomes. Clinical features such as white blood cell count and blast percentage are related to the subclonal abundance of mutations like TP53 and IDH1.
NATURE COMMUNICATIONS
(2021)
Review
Pharmacology & Pharmacy
Cindy M. Pabon, Hussein A. Abbas, Marina Konopleva
Summary: As our understanding of the intricate pathophysiology of LSCs continues to grow, it is clear that targeting such heterogenous cells successfully will require a thoughtful and multi-modal approach.
EXPERT OPINION ON THERAPEUTIC TARGETS
(2022)
Review
Infectious Diseases
Kristin olfarnes Storhaug, Dag Harald Skutlaberg, Bent Are Hansen, Hakon Reikvam, Oystein Wendelbo
Summary: Acute leukemias pose a high risk of infection, particularly bloodstream infections caused by Enterobacteriaceae, including carbapenem-resistant strains. Managing these infections is challenging due to limited clinical trials, antibiotic options, and potential side effects. Antibiotic stewardship is crucial to prevent the spread of resistant organisms while ensuring appropriate treatment for neutropenic infected patients.
Article
Oncology
Giorgia Simonetti, Davide Angeli, Elisabetta Petracci, Eugenio Fonzi, Susanna Vedovato, Alessandra Sperotto, Antonella Padella, Martina Ghetti, Anna Ferrari, Valentina Robustelli, Rosa Di Liddo, Maria Teresa Conconi, Cristina Papayannidis, Claudio Cerchione, Michela Rondoni, Annalisa Astolfi, Emanuela Ottaviani, Giovanni Martinelli, Michele Gottardi
Summary: ADM expression in AML is associated with a stem cell phenotype, inflammatory signatures, and genes related to immunosuppression, all contributing to therapy resistance and disease relapse.
FRONTIERS IN ONCOLOGY
(2021)
Article
Medicine, Research & Experimental
Na Man, Gloria Mas, Daniel L. Karl, Jun Sun, Fan Liu, Qin Yang, Miguel Torres-Martin, Hidehiro Itonaga, Concepcion Martinez, Shi Chen, Ye Xu, Stephanie Duffort, Pierre-Jacques Hamard, Chuan Chen, Beth E. Zucconi, Luisa Cimmino, Feng-Chun Yang, Mingjiang Xu, Philip A. Cole, Maria E. Figueroa, Stephen D. Nimer
Summary: This study identified a tumor suppressor role of the acetyltransferase p300 in MDS, with loss of p300 enhancing HSPC proliferation and self-renewal, ultimately increasing leukemogenicity. Mechanistically, loss of p300 altered gene expression and promoted leukemia development, while activating p300 activity countered these effects. This suggests a potential therapeutic application of p300 activators in treating MDS with TET2 mutations.
