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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 -
Acute myelogenous leukemia - current recommendations and approaches in molecular-genetic assessment.Romanian Journal of Internal Medicine =... Jun 2022Acute myelogenous leukemia is a multi-step hematological malignancy, affecting function, growth, proliferation and cell cycle of myeloid precursors. Overall assessment... (Review)
Review
Acute myelogenous leukemia is a multi-step hematological malignancy, affecting function, growth, proliferation and cell cycle of myeloid precursors. Overall assessment of patients with the disease requires among everything else, a comprehensive investigation of the genetic basis through various methods such as cytogenetic and molecular-genetic ones. This clarification provides diagnostic refinement and carries prognostic and predictive value in respect of essential therapeutic choices.With this review of the literature, we focus on summarizing the latest recommendations and preferred genetic methods, as well as on emphasizing on their general benefits and limitations. Since none of these methods is actually totipotent, we also aim to shed light over the often-difficult choice of appropriate genetic analyses.
Topics: Humans; Leukemia, Myeloid, Acute; Prognosis
PubMed: 35182066
DOI: 10.2478/rjim-2022-0004 -
Leukemia & Lymphoma Sep 2023The year 2023 marks the semi-centennial of the introduction of classic '7 + 3' chemotherapy for acute myeloid leukemia (AML) in 1973. It also marks the decennial of... (Review)
Review
The year 2023 marks the semi-centennial of the introduction of classic '7 + 3' chemotherapy for acute myeloid leukemia (AML) in 1973. It also marks the decennial of the first comprehensive sequencing efforts from The Cancer Genome Atlas (TCGA), which revealed that dozens of unique genes are recurrently mutated in AML genomes. Although more than 30 distinct genes have been implicated in AML pathogenesis, the current therapeutic armamentarium that is commercially available only targets and mutations, with olutasidenib as the most recent addition. This focused review spotlights management approaches that exploit the exquisite molecular dependencies of specific subsets of AML, with an emphasis on emerging therapies in the pipeline, including agents targeting -mutant cells. We summarize precision and strategic targeting of AML based on leveraging functional dependencies and explore how mechanisms involving critical gene products can inform rational therapeutic design in 2024.
Topics: Humans; Nucleophosmin; Leukemia, Myeloid, Acute; Mutation
PubMed: 37328939
DOI: 10.1080/10428194.2023.2224473 -
Frontiers in Immunology 2021Natural killer (NK) cells are prominent cytotoxic and cytokine-producing components of the innate immune system representing crucial effector cells in cancer... (Review)
Review
Natural killer (NK) cells are prominent cytotoxic and cytokine-producing components of the innate immune system representing crucial effector cells in cancer immunotherapy. Presently, various NK cell-based immunotherapies have contributed to the substantial improvement in the reconstitution of NK cells against advanced-staged and high-risk AML. Various NK cell sources, including haploidentical NK cells, adaptive NK cells, umbilical cord blood NK cells, stem cell-derived NK cells, chimeric antigen receptor NK cells, cytokine-induced memory-like NK cells, and NK cell lines have been identified. Devising innovative approaches to improve the generation of therapeutic NK cells from the aforementioned sources is likely to enhance NK cell expansion and activation, stimulate and persistence of NK cells and improve conventional treatment response of myeloid leukemia. The tumor-promoting properties of the tumor microenvironment and downmodulation of NK cellular metabolic activity in solid tumors and hematological malignancies constitute a significant impediment in enhancing the anti-tumor effects of NK cells. In this review, we discuss the current NK cell sources, highlight ongoing interventions in enhancing NK cell function, and outline novel strategies to circumvent immunosuppressive factors in the tumor microenvironment to improve the efficacy of NK cell-based immunotherapy and expand their future success in treating myeloid leukemia.
Topics: Biomarkers; Bone Marrow; Combined Modality Therapy; Cytokines; Cytotoxicity, Immunologic; Disease Management; Humans; Immunologic Factors; Immunologic Memory; Immunotherapy, Adoptive; Killer Cells, Natural; Leukemia, Myeloid; Tumor Microenvironment
PubMed: 34220833
DOI: 10.3389/fimmu.2021.683381 -
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 -
Frontiers in Immunology 2023Acute myeloid leukemia (AML) is a malignant clonal tumor originating from immature myeloid hematopoietic cells in the bone marrow with rapid progression and poor... (Review)
Review
Acute myeloid leukemia (AML) is a malignant clonal tumor originating from immature myeloid hematopoietic cells in the bone marrow with rapid progression and poor prognosis. Therefore, an in-depth exploration of the pathogenesis of AML can provide new ideas for the treatment of AML. In recent years, it has been found that exosomes play an important role in the pathogenesis of AML. Exosomes are membrane-bound extracellular vesicles (EVs) that transfer signaling molecules and have attracted a large amount of attention, which are key mediators of intercellular communication. Extracellular vesicles not only affect AML cells and normal hematopoietic cells but also have an impact on the bone marrow microenvironment and immune escape, thereby promoting the progression of AML and leading to refractory relapse. It is worth noting that exosomes and the various molecules they contain are expected to become the new markers for disease monitoring and prognosis of AML, and may also function as drug carriers and vaccines to enhance the treatment of leukemia. In this review, we mainly summarize to reveal the role of exosomes in AML pathogenesis, which helps us elucidate the application of exosomes in AML diagnosis and treatment.
Topics: Humans; Exosomes; Leukemia, Myeloid, Acute; Bone Marrow; Biomarkers; Tumor Microenvironment
PubMed: 38292478
DOI: 10.3389/fimmu.2023.1315453 -
The FEBS Journal Aug 2022It is essential to relate the biology of acute leukaemia to normal blood cell development. In this review, we discuss how modern models of haematopoiesis might inform... (Review)
Review
It is essential to relate the biology of acute leukaemia to normal blood cell development. In this review, we discuss how modern models of haematopoiesis might inform approaches to diagnosis and management of immature leukaemias, with a specific focus on T-lymphoid and myeloid cases. In particular, we consider whether next-generation analytical tools could provide new perspectives that could improve our understanding of immature blood cancer biology.
Topics: Acute Disease; Hematopoiesis; Humans; Leukemia, Myeloid, Acute
PubMed: 34028982
DOI: 10.1111/febs.16030 -
International Journal of Molecular... Nov 2022Despite many recent advances in treatment options, acute myeloid leukemia (AML) still has a high mortality rate. One important issue in optimizing outcomes for AML... (Review)
Review
Despite many recent advances in treatment options, acute myeloid leukemia (AML) still has a high mortality rate. One important issue in optimizing outcomes for AML patients lies in the limited ability to predict response to specific therapies, duration of response, and likelihood of relapse. With evolving genetic characterization and improving molecular definitions, the ability to predict outcomes and long-term prognosis is slowly improving. The majority of the currently used prognostic assessments relate to molecular and chromosomal abnormalities, as well as response to initial therapy. These risk categories, however, do not account for a large amount of the variability in AML. Laboratory techniques now utilized in the clinic extend beyond bone marrow morphology and single gene sequencing, to next-generation sequencing of large gene panels and multiparameter flow cytometry, among others. Other technologic advances, such as gene expression analysis, have yet to demonstrate enough predictive and prognostic power to be employed in clinical medicine outside of clinical trials, but may be incorporated into the clinic in the future. In this review, we discuss the utility of current biomarkers, and present novel biomarker techniques and strategies that are in development for AML patients. Measurable residual disease (MRD) is a powerful prognostic tool that is increasingly being incorporated into clinical practice, and there are some exciting emerging biomarker technologies that have the potential to improve prognostic power in AML. As AML continues to be a difficult-to-treat disease with poor outcomes in many subtypes, advances in biomarkers that lead to better treatment decisions are greatly needed.
Topics: Humans; Leukemia, Myeloid, Acute; Neoplasm, Residual; Flow Cytometry; Biomarkers; Bone Marrow
PubMed: 36498870
DOI: 10.3390/ijms232314543 -
Cells Aug 2020The nuclear receptor (NR) superfamily has been studied extensively in many solid tumors and some receptors have been targeted to develop therapies. However, their roles... (Review)
Review
The nuclear receptor (NR) superfamily has been studied extensively in many solid tumors and some receptors have been targeted to develop therapies. However, their roles in leukemia are less clear and vary considerably among different types of leukemia. Some NRs participate in mediating the differentiation of myeloid cells, making them attractive therapeutic targets for myeloid leukemia. To date, the success of all- retinoic acid (ATRA) in treating acute promyelocytic leukemia (APL) remains a classical and unsurpassable example of cancer differentiation therapy. ATRA targets retinoic acid receptor (RAR) and forces differentiation and/or apoptosis of leukemic cells. In addition, ligands/agonists of vitamin D receptor (VDR) and peroxisome proliferator-activated receptor (PPAR) have also been shown to inhibit proliferation, induce differentiation, and promote apoptosis of leukemic cells. Encouragingly, combining different NR agonists or the addition of NR agonists to chemotherapies have shown some synergistic anti-leukemic effects. This review will summarize recent research findings and discuss the therapeutic potential of selected NRs in acute and chronic myeloid leukemia, focusing on RAR, VDR, PPAR, and retinoid X receptor (RXR). We believe that more mechanistic studies in this field will not only shed new lights on the roles of NRs in leukemia, but also further expand the clinical applications of existing therapeutic agents targeting NRs.
Topics: Cell Differentiation; Cell Line, Tumor; Humans; Leukemia, Myeloid; Receptors, Cytoplasmic and Nuclear
PubMed: 32824945
DOI: 10.3390/cells9091921 -
Haematologica Apr 2023
Topics: Humans; Leukemia, Myeloid, Acute; Induction Chemotherapy
PubMed: 35861019
DOI: 10.3324/haematol.2022.281506