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Medicina Clinica Nov 2018Acute myeloid leukaemia is the most common form of acute leukaemia, and its incidence increases with age. The disease derives from a transformed multipotent malignant... (Review)
Review
Acute myeloid leukaemia is the most common form of acute leukaemia, and its incidence increases with age. The disease derives from a transformed multipotent malignant haematopoietic stem cell that acquires consequent genomic alterations. The identification of recurrent cytogenetic anomalies associated with different patterns of acute myeloid leukaemia clinical presentation has led to the incorporation of genetic markers in clinical decision-making. In addition, the observation that these anomalies may mark therapeutic responses and relapse and survival rates have been incorporated into the World Health Organisation's recent molecular classification and stratification and the European Leukaemia Net, with the aim of creating prognostic categories that help rationalise better diagnosis, prognosis, re-evaluation of the disease and the combination of therapeutic protocols in order to increase the survival rate of these patients.
Topics: Humans; Leukemia, Myeloid, Acute; Mutation
PubMed: 29895422
DOI: 10.1016/j.medcli.2018.05.002 -
Lancet (London, England) Nov 2006Acute myeloid leukaemia (AML) is a heterogeneous clonal disorder of haemopoietic progenitor cells and the most common malignant myeloid disorder in adults. The median... (Review)
Review
Acute myeloid leukaemia (AML) is a heterogeneous clonal disorder of haemopoietic progenitor cells and the most common malignant myeloid disorder in adults. The median age at presentation for patients with AML is 70 years. In the past few years, research in molecular biology has been instrumental in deciphering the pathogenesis of the disease. Genetic defects are thought to be the most important factors in determining the response to chemotherapy and outcome. Whereas significant progress has been made in the treatment of younger adults, the prospects for elderly patients have remained dismal, with median survival times of only a few months. This difference is related to comorbidities associated with ageing and to disease biology. Current efforts in clinical research focus on the assessment of targeted therapies. Such new approaches will probably lead to an increase in the cure rate.
Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Female; Humans; Leukemia, Myeloid; Male; Middle Aged; Prognosis; Stem Cell Transplantation
PubMed: 17126723
DOI: 10.1016/S0140-6736(06)69780-8 -
Annals of Oncology : Official Journal... Jun 2020
Topics: Adult; Follow-Up Studies; Humans; Leukemia, Myeloid, Acute
PubMed: 32171751
DOI: 10.1016/j.annonc.2020.02.018 -
British Journal of Haematology Jan 2020The field of acute myeloid leukaemia (AML) diagnostics, initially based solely on morphological assessment, has integrated more and more disciplines. Today,... (Review)
Review
The field of acute myeloid leukaemia (AML) diagnostics, initially based solely on morphological assessment, has integrated more and more disciplines. Today, state-of-the-art AML diagnostics relies on cytomorphology, cytochemistry, immunophenotyping, cytogenetics and molecular genetics. Only the integration of all of these methods allows for a comprehensive and complementary characterisation of each case, which is prerequisite for optimal AML diagnosis and management. Here, we will review why multidisciplinary diagnostics is mandatory today and will gain even more importance in the future, especially in the context of precision medicine. We will discuss ideas and strategies that are likely to shape and improve multidisciplinary diagnostics in AML and may even overcome some of today's gold standards. This includes recent technical advances that provide genome-wide molecular insights. The enormous amount of data obtained by these latter techniques represents a great challenge, but also a unique chance. We will reflect on how this increase in knowledge can be incorporated into the routine to pave the way for personalised medicine in AML.
Topics: Cytogenetic Analysis; Genome-Wide Association Study; Humans; Immunophenotyping; Leukemia, Myeloid, Acute; Precision Medicine
PubMed: 31808952
DOI: 10.1111/bjh.16360 -
Cellular & Molecular Immunology Nov 2018Acute myeloid leukaemia (AML) is a blood/bone marrow cancer originating from myeloid cell precusors capable of self-renewing. AML cells implement biochemical mechanisms... (Review)
Review
Acute myeloid leukaemia (AML) is a blood/bone marrow cancer originating from myeloid cell precusors capable of self-renewing. AML cells implement biochemical mechanisms which allow them not only to survive, but also to successfully escape immune surveillance. ln this work, we discuss crucial molecular mechanisms used by human AML cells in order to evade immune attack.
Topics: Humans; Leukemia, Myeloid, Acute; Tumor Escape
PubMed: 29872115
DOI: 10.1038/s41423-018-0047-6 -
Seminars in Hematology Apr 2006The biologic and epidemiologic study of acute myeloid leukaemia (AML) in the elderly is in its infancy. Most epidemiologic data attempting to ascertain the etiology of... (Review)
Review
The biologic and epidemiologic study of acute myeloid leukaemia (AML) in the elderly is in its infancy. Most epidemiologic data attempting to ascertain the etiology of AML have been obtained from younger cohorts or patients with therapy-related AML. The increasing prevalence of deletional and complex karyotypes in elderly AML patients implies a cumulative genotoxicity over time for this subgroup, given the similar spectrum of abnormalities following exposure to known genotoxic agents such as alkylating chemotherapeutic drugs. Exposure to benzene, radiation, and tobacco smoke are clear but weak risk factors for AML. Polymorphic variants in several genes responsible for genomic protection and integrity are now also weak risk factors for AML. Future epidemiologic studies should correlate exposure data with well-defined biologic subtypes of AML.
Topics: Acute Disease; Aged; Environmental Exposure; Humans; Leukemia, Myeloid; Molecular Epidemiology; Neoplasms, Second Primary
PubMed: 16616041
DOI: 10.1053/j.seminhematol.2006.01.005 -
International Journal of Molecular... Jun 2022Acute myeloid leukaemia (AML) is defined as a malignant disorder of the bone marrow (BM) that is characterised by the clonal expansion and differentiation arrest of...
Acute myeloid leukaemia (AML) is defined as a malignant disorder of the bone marrow (BM) that is characterised by the clonal expansion and differentiation arrest of myeloid progenitor cells [...].
Topics: Bone Marrow; Bone Marrow Cells; Humans; Leukemia, Myeloid, Acute
PubMed: 35682932
DOI: 10.3390/ijms23116251 -
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 -
British Journal of Haematology Nov 2012Although acute myeloid leukaemia (AML) has long been recognized for its morphological and cytogenetic heterogeneity, recent high-resolution genomic profiling has... (Review)
Review
Although acute myeloid leukaemia (AML) has long been recognized for its morphological and cytogenetic heterogeneity, recent high-resolution genomic profiling has demonstrated a complexity even greater than previously imagined. This complexity can be seen in the number and diversity of genetic alterations, epigenetic modifications, and characteristics of the leukaemic stem cells. The broad range of abnormalities across different AML subtypes suggests that improvements in clinical outcome will require the development of targeted therapies for each subtype of disease and the design of novel clinical trials to test these strategies. It is highly unlikely that further gains in long-term survival rates will be possible by mere intensification of conventional chemotherapy. In this review, we summarize recent studies that provide new insight into the genetics and biology of AML, discuss risk stratification and therapy for this disease, and profile some of the therapeutic agents currently under investigation.
Topics: Adolescent; Child; Child, Preschool; Humans; Leukemia, Myeloid, Acute; Prognosis; Young Adult
PubMed: 22966788
DOI: 10.1111/bjh.12040 -
British Journal of Haematology Mar 2018
Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Neoplasms; Eye Neoplasms; Female; Humans; Leukemia, Myeloid; Magnetic Resonance Imaging; Male; Middle Aged; Young Adult
PubMed: 27879987
DOI: 10.1111/bjh.14430