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Best Practice & Research. Clinical... Dec 2023The goal of a disease classification system is (or should be) to provide a tool for researchers and clinicians to study and treat the disease. The last decade has seen a... (Review)
Review
The goal of a disease classification system is (or should be) to provide a tool for researchers and clinicians to study and treat the disease. The last decade has seen a markedly improved understanding of the pathophysiology of acute myeloid leukemia (AML), the development of new methods to measure the disease, and approval by the Food and Drug Administration (FDA) of at least ten new therapies targeted to its treatment. In response, in 2022 one updated and one new AML classification system were published. In the same year, the European LeukemiaNet updated their recommendations about how to incorporate the advances in diagnosis and treatment into the risk stratification of AML and its treatment. The following discussion summarizes the highlights of these changes and offers an opinion of how well these changes meet the goal of aiding researchers and clinicians in the study and treatment of AML.
Topics: United States; Humans; Leukemia, Myeloid, Acute; World Health Organization
PubMed: 38092471
DOI: 10.1016/j.beha.2023.101518 -
Cells Nov 2019Acute myeloid leukaemia (AML) is a group of malignant diseases of the haematopoietic system. AML occurs as the result of mutations in haematopoietic stem/progenitor... (Review)
Review
Acute myeloid leukaemia (AML) is a group of malignant diseases of the haematopoietic system. AML occurs as the result of mutations in haematopoietic stem/progenitor cells, which upregulate Wnt signalling through a variety of mechanisms. Other mechanisms of Wnt activation in AML have been described such as Wnt antagonist inactivation through promoter methylation. Wnt signalling is necessary for the maintenance of leukaemic stem cells. Several molecules involved in or modulating Wnt signalling have a prognostic value in AML. These include: β-catenin, LEF-1, phosphorylated-GSK3β, PSMD2, PPARD, XPNPEP, sFRP2, RUNX1, AXIN2, PCDH17, CXXC5, LLGL1 and PTK7. Targeting Wnt signalling for tumour eradication is an approach that is being explored in haematological and solid tumours. A number of preclinical studies confirms its feasibility, albeit, so far no reliable clinical trial data are available to prove its utility and efficacy.
Topics: Animals; Biomarkers; Disease Management; Disease Susceptibility; Humans; Leukemia, Myeloid, Acute; Molecular Targeted Therapy; Prognosis; Wnt Signaling Pathway
PubMed: 31703382
DOI: 10.3390/cells8111403 -
European Journal of Haematology Jun 2022
Topics: Humans; Intracranial Hemorrhages; Leukemia, Myeloid, Acute
PubMed: 35202486
DOI: 10.1111/ejh.13761 -
Current Oncology Reports Oct 2020Acute myeloid leukemia (AML) is a costly disease, and its impact is greater in developing countries (DC). We will review the current concept of what are DC, compare the... (Review)
Review
PURPOSE OF REVIEW
Acute myeloid leukemia (AML) is a costly disease, and its impact is greater in developing countries (DC). We will review the current concept of what are DC, compare the differences in the epidemiology and economic burden of this disease between developed and DC, and finally, analyze the barriers and possible solutions that DC should implement to achieve better results.
RECENT FINDINGS
DC is a frequently misunderstood name. The way we use to measure human development is changing, and multidimension metrics better define what are DC. With this in mind, we show the differences in the AML epidemiology and the impact of economic burden in DC. We analyze the barriers to access therapy from a clinician point of view, to show that most DC shared similar challenges but with a diverse healthcare structure. Finally, we provide several possible solutions for a more integrated and timely treatment that allows better results not only in terms of survival but with a better quality of life. The economic burden of AML treatment in DC is high, and the results are poor. It is crucial to face this challenge and propose new treatment approaches to achieve better results.
Topics: Cost of Illness; Developing Countries; Health Services Accessibility; Humans; Leukemia, Myeloid, Acute; Quality of Life
PubMed: 33025161
DOI: 10.1007/s11912-020-00987-8 -
European Journal of Immunology Jan 2022Acute myeloid leukemia (AML) is a highly aggressive disease with high relapse and mortality rates. Recent years have shown a surge in novel therapeutic development for... (Review)
Review
Acute myeloid leukemia (AML) is a highly aggressive disease with high relapse and mortality rates. Recent years have shown a surge in novel therapeutic development for AML, both in clinical and preclinical stages. These developments include targeted therapies based on AML-specific molecular signatures as well as more general immune modulation and vaccination studies. In this review, we will explore the evolving arena of AML therapy and suggest some intriguing connections between immune system modulation and targeted therapy. Improved understanding of the immune system involvement in various stages of the disease and the crosstalk between immune effectors, targeted therapy, and AML cells can provide a better framework for designing the next generation of AML therapies.
Topics: Humans; Leukemia, Myeloid, Acute; Molecular Targeted Therapy
PubMed: 34648664
DOI: 10.1002/eji.202048945 -
Haematologica Dec 2022Considerable progress has been made in the past several years in the scientific understanding of, and available treatments for, acute myeloid leukemia (AML). Achievement... (Review)
Review
Considerable progress has been made in the past several years in the scientific understanding of, and available treatments for, acute myeloid leukemia (AML). Achievement of a conventional remission, evaluated cytomorphologically via small bone marrow samples, is a necessary but not sufficient step toward cure. It is increasingly appreciated that molecular or immunophenotypic methods to identify and quantify measurable residual disease (MRD) - populations of leukemia cells below the cytomorphological detection limit - provide refined information on the quality of response to treatment and prediction of the risk of AML recurrence and leukemia-related deaths. The principles and practices surrounding MRD remain incompletely determined however and the genetic and immunophenotypic heterogeneity of AML may prevent a one-sizefits- all approach. Here, we review the current approaches to MRD testing in AML, discuss strengths and limitations, highlight recent technological advances that may improve such testing, and summarize ongoing initiatives to generate the clinical evidence needed to advance the use of MRD testing in patients with AML.
Topics: Humans; Neoplasm, Residual; Leukemia, Myeloid, Acute; Immunophenotyping
PubMed: 36453518
DOI: 10.3324/haematol.2022.282034 -
British Journal of Pharmacology Jan 2024Acute myeloid leukaemia (AML) continues to have a poor prognosis, warranting new therapeutic strategies. The bone marrow (BM) microenvironment consists of niches that... (Review)
Review
Acute myeloid leukaemia (AML) continues to have a poor prognosis, warranting new therapeutic strategies. The bone marrow (BM) microenvironment consists of niches that interact with not only normal haematopoietic stem cells (HSC) but also leukaemia cells like AML. There are many adhesion molecules in the BM microenvironment; therein, integrins have been of central interest. AML cells express integrins that bind to ligands in the microenvironment, enabling adhesion of leukaemia cells in the microenvironment, thereby initiating intracellular signalling pathways that are associated with cell migration, cell proliferation, survival, and drug resistance that has been described to mediate cell adhesion-mediated drug resistance (CAM-DR). Identifying and targeting integrins in AML to interrupt interactions with the microenvironment have been pursued as a strategy to overcome CAM-DR. Here, we focus on the BM microenvironment and review the role of integrins in CAM-DR of AML and discuss integrin-targeting strategies. LINKED ARTICLES: This article is part of a themed issue on Cancer Microenvironment and Pharmacological Interventions. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v181.2/issuetoc.
Topics: Humans; Integrins; Leukemia, Myeloid, Acute; Bone Marrow; Hematopoietic Stem Cells; Cell Adhesion Molecules; Tumor Microenvironment
PubMed: 37258706
DOI: 10.1111/bph.16149 -
British Journal of Haematology Jan 2020Modern management of acute myeloid leukaemia (AML) relies on the integration of phenotypic and genetic data to assign classification, establish prognosis, enhance... (Review)
Review
Modern management of acute myeloid leukaemia (AML) relies on the integration of phenotypic and genetic data to assign classification, establish prognosis, enhance monitoring and guide treatment. The prism through which we can now disperse a patient's leukaemia, interpret and apply our understanding has fundamentally changed since the completion of the first whole-genome sequencing (WGS) of an AML patient in 2008 and where possible, many clinicians would now prefer to delay treatment decisions until the karyotype and genetic status of a new patient is known. The success of global sequencing initiatives such as The Cancer Genome Atlas (TCGA) have brought us significantly closer to cataloguing the full spectrum of coding mutations involved in human malignancy. Indeed, genetic capability has raced ahead of our capacity to apply much of this knowledge into clinical practice and we are in the peculiar position of having routine access to genetic information on an individual patient's leukaemia that cannot be reliably interpreted or utilised. This is a measure of how rapid the progress has been, and this rate of change is likely to continue into the foreseeable future as research intensifies on the non-coding genome and the epigenome, as we scrutinise disease at a single cell level, and as initiatives like Beat AML and the Harmony Alliance progress. In this review, we will examine how interrogation of the coding genome is revolutionising our understanding of AML and improving our ability to underscore differences between paediatric and adult onset, sporadic and inherited forms of disease. We will look at how this knowledge is informing improvements in outcome prediction and the development of novel treatments, bringing us a step closer to personalised therapy for myeloid malignancy.
Topics: Databases, Genetic; Epigenome; Genome, Human; Humans; Leukemia, Myeloid, Acute; Mutation; Whole Genome Sequencing
PubMed: 31863468
DOI: 10.1111/bjh.16356 -
Clinical Medicine (London, England) May 2022Acute leukaemia is characterised by uncontrolled expansion of immature leukocytes, either myeloid or lymphoid progenitors, leading to acute myeloid leukaemia (AML) and...
Acute leukaemia is characterised by uncontrolled expansion of immature leukocytes, either myeloid or lymphoid progenitors, leading to acute myeloid leukaemia (AML) and acute lymphoid leukaemia (ALL), respectively. If left untreated, it is life-threatening and can lead to death within weeks. When acute leukaemia is suspected, urgent haematology input should be sought. Appropriate investigations are needed promptly to confirm diagnosis and start treatment. A multidisciplinary approach is vital to ensure appropriate management.
Topics: Acute Disease; Humans; Leukemia, Myeloid, Acute
PubMed: 35584840
DOI: 10.7861/clinmed.2022-0149 -
Seminars in Cancer Biology Feb 2020The development of a myeloid neoplasm is a step-wise process that originates from leukemic stem cells (LSC) and includes pre-leukemic stages, overt leukemia and a... (Review)
Review
The development of a myeloid neoplasm is a step-wise process that originates from leukemic stem cells (LSC) and includes pre-leukemic stages, overt leukemia and a drug-resistant terminal phase. Organ-invasion may occur in any stage, but is usually associated with advanced disease and a poor prognosis. Sometimes, extra-medullary organ invasion shows a metastasis-like or even sarcoma-like destructive growth of neoplastic cells in local tissue sites. Examples are myeloid sarcoma, mast cell sarcoma and localized blast phase of chronic myeloid leukemia. So far, little is known about mechanisms underlying re-distribution and extramedullary dissemination of LSC in myeloid neoplasms. In this article, we discuss mechanisms through which LSC can mobilize out of the bone marrow niche, can transmigrate from the blood stream into extramedullary organs, can invade local tissue sites and can potentially create or support the formation of local stem cell niches. In addition, we discuss strategies to interfere with LSC expansion and organ invasion by targeted drug therapies.
Topics: Animals; Biomarkers; Bone Marrow; Cell Communication; Cell Movement; Humans; Immunophenotyping; Leukemia, Myeloid; Neoplasm Staging; Neoplastic Stem Cells; Phenotype; Recurrence; Transendothelial and Transepithelial Migration; Tumor Microenvironment
PubMed: 31408723
DOI: 10.1016/j.semcancer.2019.07.025