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Best Practice & Research. Clinical... Dec 2022The advances and progress in the understanding and management of acute leukemia and myelodysplasia continue to occur at an exponential rate. While this has led to more... (Review)
Review
The advances and progress in the understanding and management of acute leukemia and myelodysplasia continue to occur at an exponential rate. While this has led to more therapy options, clinicians and researchers are now facing more challenges in terms of clinical decision-making and more unanswered questions. This paper has outlined some conundrums in acute leukemia and myelodysplasia, and the efforts that are underway to address these.
Topics: Humans; Myelodysplastic Syndromes; Leukemia, Myeloid, Acute; Acute Disease
PubMed: 36517125
DOI: 10.1016/j.beha.2022.101415 -
Haematologica Apr 2023
Topics: Humans; Leukemia, Myeloid, Acute
PubMed: 36005564
DOI: 10.3324/haematol.2022.281742 -
International Journal of Cancer May 2022Acute myeloid leukemia (AMLs), as the name suggests, often develop suddenly and are very progressive forms of cancer. Unlike in acute promyelocytic leukemia, a subtype... (Review)
Review
Acute myeloid leukemia (AMLs), as the name suggests, often develop suddenly and are very progressive forms of cancer. Unlike in acute promyelocytic leukemia, a subtype of AML, the outcomes in most other AMLs remain poor. This is mainly attributed to the acquired drug resistance and lack of targeted therapy. Different studies across laboratories suggest that the cellular mechanisms to impart therapy resistance are often very dynamic and should be identified in a context-specific manner. Our review highlights the progress made so far in identifying the different cellular mechanisms of mutation-independent therapy resistance in AML. It reiterates that for more effective outcomes cancer therapies should acquire a more tailored approach where the protective interactions between the cancer cells and their niches are identified and targeted.
Topics: Drug Resistance; Humans; Leukemia, Myeloid, Acute; Leukemia, Promyelocytic, Acute; Mutation; Tumor Microenvironment
PubMed: 34921734
DOI: 10.1002/ijc.33908 -
Leukemia & Lymphoma 2023Acute myeloid leukemia (AML) is a hematological malignancy with strong heterogeneity. Immune disorders are a feature of various malignancies, including AML. Interleukins... (Review)
Review
Acute myeloid leukemia (AML) is a hematological malignancy with strong heterogeneity. Immune disorders are a feature of various malignancies, including AML. Interleukins (ILs) and other cytokines participate in a series of biological processes of immune disorders in the microenvironment, and serve as a bridge for communication between various cellular components in the immune system. The role of ILs in AML is complex and pleiotropic. It can not only play an anti-AML role by enhancing anti-leukemia immunity and directly inducing AML cell apoptosis, but also promote the growth, proliferation and drug resistance of AML. These properties of ILs can be used to explore their potential efficacy in disease monitoring, prognosis assessment, and development of new treatment strategies for AML. This review aims to clarify some of the complex roles of ILs in AML and their clinical applications.
Topics: Humans; Leukemia, Myeloid, Acute; Interleukins; Cytokines; Immune System Diseases; Tumor Microenvironment
PubMed: 37259867
DOI: 10.1080/10428194.2023.2218508 -
Hematology/oncology Clinics of North... Apr 2020Secondary acute myeloid leukemia (sAML) is a complex diagnosis that includes AML caused by either an antecedent hematologic disease (AML-AHD) or from previous treatment... (Review)
Review
Secondary acute myeloid leukemia (sAML) is a complex diagnosis that includes AML caused by either an antecedent hematologic disease (AML-AHD) or from previous treatment with chemotherapy or radiation. This disease carries a poor prognosis and is historically chemorefractory; additionally, often patients are ineligible for standard chemotherapy because of advanced age and other comorbidities. The advances of molecular diagnostics and reclassification of World Health Organization criteria have aided in the categorization of this disease. This article describes the etiology and pathophysiology of sAML, and delves into past successful treatments as well as promising new treatments.
Topics: Biomarkers, Tumor; Combined Modality Therapy; Disease Management; Disease Susceptibility; Genetic Predisposition to Disease; Humans; Incidence; Leukemia, Myeloid, Acute; Prognosis; Treatment Outcome
PubMed: 32089222
DOI: 10.1016/j.hoc.2019.11.003 -
Current Treatment Options in Oncology Jan 2020Acute myeloid leukemia (AML) disease prognosis is poor and there is a high risk of chemo-resistant relapse for both young and old patients. Thus, there is a demand for... (Review)
Review
Acute myeloid leukemia (AML) disease prognosis is poor and there is a high risk of chemo-resistant relapse for both young and old patients. Thus, there is a demand for alternative and target-specific drugs to improve the 5-year survival rate. Current treatment mainstays include chemotherapy, or mutation-specific targeting molecules including FLT3 inhibitors, IDH inhibitors, and monoclonal antibodies. Efforts to devise new, targeted therapy have included recent advances in methods for high-throughput genomic screening and the availability of computer-assisted techniques for the design of novel agents predicted to specifically inhibit mutant molecules involved in leukemogenesis. Crosstalk between the leukemia cells and the bone marrow microenvironment through cell surface molecules, such as the integrins αvβ3 and αvβ5, might influence drug response and AML progression. This review article focuses on current AML treatment options, new AML targeted therapies, the role of integrins in AML progression, and a potential therapeutic agent-integrin αvβ3 antagonist.
Topics: Biomarkers, Tumor; Combined Modality Therapy; Disease Management; Disease Susceptibility; Humans; Leukemia, Myeloid, Acute; Molecular Targeted Therapy; Mutation; Prognosis; Standard of Care; Treatment Outcome
PubMed: 31933183
DOI: 10.1007/s11864-019-0694-6 -
Trends in Cell Biology Jun 2023Acute myeloid leukemia (AML) is a malignant disease of myeloid precursors. Somatic mutations have long been accepted as drivers of this malignancy. Over the past decade,... (Review)
Review
Acute myeloid leukemia (AML) is a malignant disease of myeloid precursors. Somatic mutations have long been accepted as drivers of this malignancy. Over the past decade, unique mitochondrial and metabolic dependencies of AML and AML stem cells have been identified, including a reliance on oxidative phosphorylation. More recently, metabolic enzymes have demonstrated noncanonical roles in regulating gene expression in AML, controlling cell differentiation and stemness. These mitochondrial and metabolic adaptations occur independent of underlying genomic abnormalities and contribute to chemoresistance and relapse. In this opinion article, we discuss the current understanding of AML pathogenesis and whether mitochondrial and metabolic abnormalities drive leukemogenesis or are a non-contributory phenotype.
Topics: Humans; Leukemia, Myeloid, Acute; Cell Differentiation; Oxidative Phosphorylation
PubMed: 36481232
DOI: 10.1016/j.tcb.2022.11.004 -
Current Oncology Reports Jun 2020The purpose of this review is to summarize the current literature on the presentation, diagnosis, and treatment options available for extramedullary (EM) manifestations... (Review)
Review
PURPOSE OF REVIEW
The purpose of this review is to summarize the current literature on the presentation, diagnosis, and treatment options available for extramedullary (EM) manifestations of leukemia including myeloid sarcoma (MS) and leukemia cutis (LC).
RECENT FINDINGS
Advanced imaging using 18FDG-PET/CT is an effective screening tool for EM manifestations of leukemia. The role of radiation therapy has been more clearly delineated in the treatment of both MS and LC. FDA-approved targeted agents have improved outcomes in patients with AML but have not demonstrated improvements specifically for EM; however, a checkpoint inhibitor, Ipilimumab, holds promise in impacting local control for the treatment of AML-related EM. EM manifestations of leukemia pose significant therapeutic challenges. Treatment of EM is predicated on multiple factors including the presence of concomitant bone marrow involvement, AML-risk classification, and timing of presentation at initial diagnosis or relapse following systemic therapy.
Topics: Humans; Leukemia, Myeloid, Acute; Prognosis; Sarcoma, Myeloid; Skin Neoplasms
PubMed: 32577912
DOI: 10.1007/s11912-020-00919-6 -
Leukemia Dec 2021Children with Down syndrome are at an elevated risk of leukemia, especially myeloid leukemia (ML-DS). This malignancy is frequently preceded by transient abnormal... (Review)
Review
Children with Down syndrome are at an elevated risk of leukemia, especially myeloid leukemia (ML-DS). This malignancy is frequently preceded by transient abnormal myelopoiesis (TAM), which is self-limited expansion of fetal liver-derived megakaryocyte progenitors. An array of international studies has led to consensus in treating ML-DS with reduced-intensity chemotherapy, leading to excellent outcomes. In addition, studies performed in the past 20 years have revealed many of the genetic and epigenetic features of the tumors, including GATA1 mutations that are arguably associated with all cases of both TAM and ML-DS. Despite these advances in understanding the clinical and biological aspects of ML-DS, little is known about the mechanisms of relapse. Upon relapse, patients face a poor outcome, and there is no consensus on treatment. Future studies need to be focused on this challenging aspect of leukemia in children with DS.
Topics: Down Syndrome; GATA1 Transcription Factor; Humans; Leukemia, Myeloid; Mutation
PubMed: 34518645
DOI: 10.1038/s41375-021-01414-y -
British Journal of Haematology Jan 2020Comprehensive cataloguing of the acute myeloid leukaemia (AML) genome has revealed a high frequency of mutations and deletions in epigenetic factors that are frequently... (Review)
Review
Comprehensive cataloguing of the acute myeloid leukaemia (AML) genome has revealed a high frequency of mutations and deletions in epigenetic factors that are frequently linked to treatment resistance and poor patient outcome. In this review, we discuss how the epigenetic mechanisms that underpin normal haematopoiesis are subverted in AML, and in particular how these processes are altered in childhood and adolescent leukaemias. We also provide a brief summary of the burgeoning field of epigenetic-based therapies, and how AML treatment might be improved through provision of better conceptual frameworks for understanding the pleiotropic molecular effects of epigenetic disruption.
Topics: Adolescent; Child; Drug Resistance, Neoplasm; Epigenesis, Genetic; Hematopoiesis; Humans; Leukemia, Myeloid, Acute; Mutation
PubMed: 31804725
DOI: 10.1111/bjh.16361