Article
Medicine, General & Internal
Courtney D. Dinardo, Harry P. Erba, Sylvie D. Freeman, Andrew H. Wei
Summary: Progress in acute myeloid leukaemia treatment has seen significant improvements in scientific understanding, prognostication tools, risk assessments, and incorporation of measurable residual disease into risk assessments. Recent updates in classification and recommendations by organizations such as WHO, ICC, and European LeukemiaNet have provided enhanced guidance for prognostic stratification and treatment response assessment. There have also been advancements in treatment options, leading to improved outcomes for both newly diagnosed and relapsed patients.
Article
Multidisciplinary Sciences
Jie Xu, Fan Song, Huijue Lyu, Mikoto Kobayashi, Baozhen Zhang, Ziyu Zhao, Ye Hou, Xiaotao Wang, Yu Luan, Bei Jia, Lena Stasiak, Josiah Hiu-yuen Wong, Qixuan Wang, Qi Jin, Qiushi Jin, Yihao Fu, Hongbo Yang, Ross C. Hardison, Sinisa Dovat, Leonidas C. Platanias, Yarui Diao, Yue Yang, Tomoko Yamada, Aaron D. Viny, Ross L. Levine, David Claxton, James R. Broach, Hong Zheng, Feng Yue
Summary: This study uses Hi-C and whole-genome sequencing to analyze samples from AML patients and healthy donors, revealing recurrent and subtype-specific alterations in chromatin structure and loops. Functional validation and manipulation of DNA methylation further highlight the role of repressive loops and hijacked cis elements in AML.
Article
Multidisciplinary Sciences
Gabriele Casirati, Andrea Cosentino, Adele Mucci, Mohammed Salah Mahmoud, Iratxe Ugarte Zabala, Jing Zeng, Scott B. Ficarro, Denise Klatt, Christian Brendel, Alessandro Rambaldi, Jerome Ritz, Jarrod A. Marto, Danilo Pellin, Daniel E. Bauer, Scott A. Armstrong, Pietro Genovese
Summary: Epitope engineering of donor haematopoietic stem/progenitor cells endows haematopoietic lineages with selective resistance to CAR T cells or monoclonal antibodies, without affecting protein function or regulation, enabling the targeting of genes that are essential for leukaemia survival and reducing the risk of tumour immune escape.
Review
Pharmacology & Pharmacy
Heather A. Ogana, Samantha Hurwitz, Nathan Wei, Eliana Lee, Kayla Morris, Karina Parikh, Yong-Mi Kim
Summary: Acute myeloid leukaemia (AML) has a poor prognosis and new therapeutic strategies are needed. The bone marrow (BM) microenvironment contains niches that interact with both normal haematopoietic stem cells and AML cells. Integrins, which are adhesion molecules in the BM microenvironment, play a central role in AML. AML cells express integrins that bind to ligands in the microenvironment, leading to adhesion, intracellular signalling, and drug resistance. Targeting integrins in AML to disrupt interactions with the microenvironment is being explored as a strategy to overcome drug resistance.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Review
Medicine, General & Internal
Jorge Cortes, Carolina Pavlovsky, Susanne Saussele
Summary: Tyrosine-kinase inhibitors have significantly altered the natural course of chronic myeloid leukaemia, allowing some patients to approach a near-normal life expectancy. Successful treatment requires understanding the patient's treatment goals, monitoring optimal response hallmarks, timely interventions, recognition of adverse events, and management of comorbidities.
Review
Pharmacology & Pharmacy
Xinrong Xiang, Rui Bao, Yu Wu, Youfu Luo
Summary: This article comprehensively reviews the role of mitochondrial proteases in acute myeloid leukemia (AML), highlighting their biological function, chemical modulators, and applicative prospects in AML.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Review
Hematology
Sabine Kayser, Mark J. Levis
Summary: Research on the pathogenic mechanisms of AML has made remarkable advances in recent years, especially in the importance of cytogenetic and molecular aberrations. The development of new compounds targeting AML at a molecular level, based on increased understanding of AML pathogenesis facilitated by next-generation sequencing, has turned many hopeful predictions into therapeutic realities.
BRITISH JOURNAL OF HAEMATOLOGY
(2022)
Article
Multidisciplinary Sciences
Mohieddin Jafari, Mehdi Mirzaie, Jie Bao, Farnaz Barneh, Shuyu Zheng, Johanna Eriksson, Caroline A. Heckman, Jing Tang
Summary: This study proposes a bipartite network modelling approach to identify effective drug combinations for the treatment of acute myeloid leukaemia. By analyzing patient and cell line drug screening data, the authors discover multi-targeted drug combinations and validate their potency and synergy through in vitro experiments.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Lauren Cairns, Katrina M. Lappin, Alexander Mutch, Ahlam Ali, Kyle B. Matchett, Ken Mills
Summary: Paediatric acute myeloid leukaemia (AML) is a complex disease with limited treatment options due to longstanding standard therapies and inadequate understanding of its biology. Recent advancements in genomic technologies have accelerated the search for new targets for paediatric AML treatment. Exploiting drug combinations through innovative screening strategies may offer new therapeutic options for paediatric AML.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Editorial Material
Hematology
Robert K. Hills
Summary: The paper by Noor et al. presents significant findings on the incidence and outcomes of patients with acute myeloid leukaemia in Afghanistan. It highlights the lower age of patients compared to the Western standard, reflecting the unique demographics of the country. These findings serve as an important initial step in identifying areas for improvement.
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Jochen Greiner, Elliott Brown, Lars Bullinger, Robert K. Hills, Vanessa Morris, Hartmut Doehner, Ken I. Mills, Barbara-ann Guinn
Summary: This study found that BIRC5 expression plays a role in the survival of AML patients, with above median levels associated with improved overall survival but not reaching statistical significance. Adjusted analyses showed a beneficial effect of high BIRC5 levels on overall survival. Additionally, decreased BIRC5 expression was associated with better clinical outcome.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Oncology
Sam Humphries, Danielle R. Bond, Zacary P. Germon, Simon Keely, Anoop K. Enjeti, Matthew D. Dun, Heather J. Lee
Summary: Hypoxia plays a role in influencing AML progression through interactions with DNA methylation, limiting the efficacy of hypomethylating agents within the hypoxic bone marrow. Co-treatments that promote cycling of AML cells within the bone marrow or encourage their dissociation from the bone marrow may be necessary for optimal outcomes in AML patients.
CLINICAL EPIGENETICS
(2023)
Review
Biochemistry & Molecular Biology
Lynn Chin, Chantelle Ye Gwen Wong, Harinder Gill
Summary: Mutations in the NPM1 gene are commonly found in AML patients, and this review explores various molecular methods for monitoring minimal residual disease (MRD) in NPM1-mutated AML. It also discusses current and potential drug therapies, as well as targeted strategies for aberrant NPM1 pathways and epigenetic regulation. The effects of stress on AML presentation and the advancement of immunotherapy are also mentioned.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Oncology
Teerna Bhattacharyya, Jonathan Bond
Summary: This review article provides an overview of how genetic alterations in AML affect the structure and function of Polycomb Repressive Complexes (PRCs), particularly focusing on PRC2 core factors. The mutations and deletions in PRC2 factors are linked to other AML-associated genetic alterations and may inform potential treatment avenues. Understanding these genetic interactions and their implications for therapy is crucial in the study of AML.
Article
Biochemistry & Molecular Biology
Courtney D. DiNardo, Hannah C. Beird, Marcos Estecio, Swanand Hardikar, Koichi Takahashi, Sarah A. Bannon, Gautam Borthakur, Elias Jabbour, Curtis Gumbs, Joseph D. Khoury, Mark Routbort, Ting Gong, Kimie Kondo, Hagop Kantarjian, Guillermo Garcia-Manero, Taiping Chen, P. Andrew Futreal
Summary: A novel germline missense mutation DNMT3A p.P709S was identified in a mother and son pair with AML, showing dominant negative effects and global DNA hypomethylation. Somatic mutations in IDH2 and DNMT3A in AML patients indicate the crucial pathogenic interaction of these genes in leukemogenesis.