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British Journal of Haematology Jan 2020Acute myeloid leukaemia (AML) is a heterogeneous disease in which prognosis is determined by cytogenetic and molecular aberrations as well as patient-related factors,... (Review)
Review
Acute myeloid leukaemia (AML) is a heterogeneous disease in which prognosis is determined by cytogenetic and molecular aberrations as well as patient-related factors, including age, prior haematologic disorders, and comorbidities. Despite the diverse disease biology, the standard of care for remission induction therapy has changed very little since its inception in 1973. Next generation sequencing has helped to increase our knowledge of the disease pathogenesis, allowing us to develop targeted and possibly more effective treatment options. Seven new agents have been approved for the treatment of AML since 2017, all of which are directed toward a specific molecular subtype or patient population. With the advent of these therapies, a more optimal, patient-specific approach rather than the historical 'one-size fits all' model can be utilised. This review will discuss the role of these novel therapies in the remission induction setting.
Topics: Disease-Free Survival; High-Throughput Nucleotide Sequencing; Humans; Leukemia, Myeloid, Acute; Precision Medicine; Remission Induction
PubMed: 31828798
DOI: 10.1111/bjh.16353 -
Bioscience Reports Apr 2022Acute myeloid leukaemia (AML) is an aggressive disease of the bone marrow with a poor prognosis. Evidence suggests long established chemotherapeutic regimens used to... (Review)
Review
Acute myeloid leukaemia (AML) is an aggressive disease of the bone marrow with a poor prognosis. Evidence suggests long established chemotherapeutic regimens used to treat AML are reaching the limits of their efficacy, necessitating the urgent development of novel targeted therapies. Canonical Wnt signalling is an evolutionary conserved cascade heavily implicated in normal developmental and disease processes in humans. For over 15 years its been known that the central mediator of this pathway, β-catenin, is dysregulated in AML promoting the emergence, maintenance, and drug resistance of leukaemia stem cells. Yet, despite this knowledge, and subsequent studies demonstrating the therapeutic potential of targeting Wnt activity in haematological cancers, β-catenin inhibitors have not yet reached the clinic. The aim of this review is to summarise the current understanding regarding the role and mechanistic dysregulation of β-catenin in AML, and assess the therapeutic merit of pharmacologically targeting this molecule, drawing on lessons from other disease contexts.
Topics: Humans; Leukemia, Myeloid, Acute; Wnt Signaling Pathway; beta Catenin
PubMed: 35352805
DOI: 10.1042/BSR20211841 -
The Lancet. Haematology May 2015
Topics: Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid
PubMed: 26688088
DOI: 10.1016/S2352-3026(15)00076-9 -
Best Practice & Research. Clinical... Mar 2001Acute myeloid leukaemia (AML) is characterized by a block in differentiation and an unregulated proliferation of myeloid progenitor cells. While the cause of AML in... (Review)
Review
Acute myeloid leukaemia (AML) is characterized by a block in differentiation and an unregulated proliferation of myeloid progenitor cells. While the cause of AML in children is unknown, risk factors that have been identified include exposure to toxins such as ethanol, pesticides and dietary topoisomerase II inhibitors, prior chemotherapy with alkylating agents or topoisomerase II inhibitors, constitutional disorders such as Down's syndrome and type I neurofibromatosis, and haematopoietic failure syndromes such as Fanconi anaemia and severe congenital neutropenia. With intensified chemotherapy including high-dose Ara-C, followed in many cases by bone marrow transplantation, and with improvements in supportive care, current survival rates approach 50%. Future advances in paediatric AML will include better risk stratification to determine optimal treatment and targeted cytotoxic therapy.
Topics: Acute Disease; Adolescent; Child; Child, Preschool; Clinical Trials as Topic; Humans; Leukemia, Myeloid; Risk Factors; Treatment Outcome
PubMed: 11355925
DOI: 10.1053/beha.2000.0117 -
Disease Models & Mechanisms Aug 2014Acute myeloid leukaemia (AML) is an uncontrolled clonal proliferation of abnormal myeloid progenitor cells in the bone marrow and blood. Advances in cancer genomics have... (Review)
Review
Acute myeloid leukaemia (AML) is an uncontrolled clonal proliferation of abnormal myeloid progenitor cells in the bone marrow and blood. Advances in cancer genomics have revealed the spectrum of somatic mutations that give rise to human AML and drawn our attention to its molecular evolution and clonal architecture. It is now evident that most AML genomes harbour small numbers of mutations, which are acquired in a stepwise manner. This characteristic, combined with our ability to identify mutations in individual leukaemic cells and our detailed understanding of normal human and murine haematopoiesis, makes AML an excellent model for understanding the principles of cancer evolution. Furthermore, a better understanding of how AML evolves can help us devise strategies to improve the therapy and prognosis of AML patients. Here, we draw from recent advances in genomics, clinical studies and experimental models to describe the current knowledge of the clonal evolution of AML and its implications for the biology and treatment of leukaemias and other cancers.
Topics: Animals; Clonal Evolution; Genetic Association Studies; Genome, Human; Humans; Leukemia, Myeloid, Acute; Mutation; Neoplastic Stem Cells
PubMed: 25056697
DOI: 10.1242/dmm.015974 -
Rheumatology (Oxford, England) Oct 2009To assess the risk factors for leukaemic transformation and myeloid leukaemia in patients with SLE. (Review)
Review
OBJECTIVE
To assess the risk factors for leukaemic transformation and myeloid leukaemia in patients with SLE.
METHODS
A national SLE cohort identified through SLE discharge diagnoses in the Swedish hospital discharge register during 1964 to 1995 (n = 6438) was linked to the national cancer register. A nested case-control study in SLE patients who developed acute or chronic myeloid leukaemia was performed with SLE patients without malignancy as controls. Medical records from cases and controls were reviewed and bone marrow specimens were re-evaluated. A Medline search of previously published cases of SLE and myeloid leukaemia was performed.
RESULTS
After confirmation of SLE diagnosis according to the ACR criteria, eight patients with SLE and myeloid leukaemia and 18 SLE controls were included in the study. Preceding leucopenia was significantly associated with leukaemia development, whereas other SLE manifestations were not. Two cases had a preceding bone marrow confirming myelodysplastic syndrome (MDS). Only two cases were significantly treated with cyclophosphamide or AZA. A Medline search resulted in only 15 previously published cases of coincident SLE and myeloid leukaemia. Preceding MDS was reported in five of these, whereas only eight had been treated with cytotoxic drugs.
CONCLUSION
Low-dose chemotherapy was not a major cause of myeloid malignancy in our population-based cohort of SLE patients nor in the reported cases from literature. Leucopenia was a risk factor for myeloid leukaemia development and an MDS was frequently seen. Therefore bone marrow investigation should be considered in SLE patients with long-standing leucopenia and anaemia.
Topics: Adolescent; Adult; Aged; Bone Marrow Examination; Epidemiologic Methods; Female; Humans; Immunosuppressive Agents; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukopenia; Lupus Erythematosus, Systemic; Male; Middle Aged; Phenotype; Sweden; Young Adult
PubMed: 19608725
DOI: 10.1093/rheumatology/kep204 -
Current Opinion in Hematology Mar 2018This review summarizes the hallmark developments in induction chemotherapy for acute myeloid leukaemia and further describes future directions in its evolution. (Review)
Review
PURPOSE OF REVIEW
This review summarizes the hallmark developments in induction chemotherapy for acute myeloid leukaemia and further describes future directions in its evolution.
RECENT FINDINGS
We describe the origin of induction chemotherapy. We also describe notable modifications and adjustments to 7+3 induction chemotherapy since its development. Finally, we describe new efforts to modify and add new agents to induction therapy, including '7+3 Plus' combinations.
SUMMARY
Induction chemotherapy remains the standard of care for the majority of patients with acute myeloid leukaemia. However, its success is limited in a subset of patients by toxicity, failure to achieve remission and potential for subsequent relapse. Novel agents such as mutant fms like tyrosine kinase 3 inhibitors, mutant isocitrate dehydrogenase inhibitors, CD33-antibody drug conjugates and liposomal formulations have demonstrated significant potential as modifications to traditional induction chemotherapy.
Topics: Animals; Antineoplastic Agents; Humans; Induction Chemotherapy; Leukemia, Myeloid, Acute
PubMed: 29337707
DOI: 10.1097/MOH.0000000000000407 -
British Medical Bulletin Oct 1996There has been considerable progress in the understanding and treatment of childhood acute myeloid leukaemia over the past two decades. In particular, cyto- and... (Review)
Review
There has been considerable progress in the understanding and treatment of childhood acute myeloid leukaemia over the past two decades. In particular, cyto- and molecular genetics offer the potential for more specific diagnosis of what is basically a heterogeneous disease. To date treatment has been based on a steady increase in cytotoxic chemotherapy with or without the addition of bone marrow transplantation. Randomised therapeutic trials are difficult to perform in what is a rare disease. The best way forward is for paediatric trial groups worldwide to collaborate in developing common, or parallel, therapeutic protocols.
Topics: Acute Disease; Bone Marrow Transplantation; Child; Child, Preschool; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Humans; Infant; Infant, Newborn; Leukemia, Myeloid; Recurrence; Remission Induction
PubMed: 9039730
DOI: 10.1093/oxfordjournals.bmb.a011581 -
Australian and New Zealand Journal of... Dec 1981
Review
Topics: Acute Disease; Adult; Bone Marrow Transplantation; Busulfan; Cell Transformation, Neoplastic; Child, Preschool; Chromosomes, Human, 21-22 and Y; Chronic Disease; Humans; Leukemia, Myeloid; Prognosis; Retrospective Studies; Splenectomy
PubMed: 7036974
DOI: 10.1111/j.1445-5994.1981.tb03547.x -
Pathology Feb 2023Molecular testing in acute myeloid leukaemia (AML) has continued to dramatically advance in recent years, facilitating the ability to detect residual disease at... (Review)
Review
Molecular testing in acute myeloid leukaemia (AML) has continued to dramatically advance in recent years, facilitating the ability to detect residual disease at exponentially lower levels. With the advent of the recently updated ELN consensus recommendations, there is increasing complexity to ordering and interpreting measurable residual disease (MRD) assays in AML. We outline the technology itself in conjunction with the relevant testing timepoints, clinically significant thresholds and potential prognostic and therapeutic significance of MRD testing for the major molecular targets in AML. This practical overview should assist haematologists in incorporating molecular MRD assays routinely into their personalised AML clinical management.
Topics: Humans; Leukemia, Myeloid, Acute; Prognosis; Neoplasm, Residual; Molecular Diagnostic Techniques
PubMed: 36503638
DOI: 10.1016/j.pathol.2022.11.003