-
Hematology (Amsterdam, Netherlands) Dec 2023to review the current diagnostic and therapeutic landscape of AML in Latin America as a reflection of other low- and middle-income countries and regions of the world.... (Review)
Review
OBJECTIVE
to review the current diagnostic and therapeutic landscape of AML in Latin America as a reflection of other low- and middle-income countries and regions of the world. Encompassing both acute promyelocytic and non-promyelocytic disease types.
METHODS
We reviewed the literature and study registries concerning epidemiological features of patients with AML/APL treated in Latin America, as well as evaluated diagnostic and genetic stratification and patient fitness assessment challenges, the importance of early mortality and supportive care capacity, intensive and non-intensive chemotherapy alternatives, consolidation, and maintenance strategies including novel agents and hematopoietic stem cell transplantation.
RESULTS
Although most of the current technologies and treatment options are available in the region, a significant fraction of patients have only limited access to them. In addition, mortality in the first weeks from diagnosis is higher in the region compared to developed countries.
CONCLUSIONS
Disparities in access to technologies, supportive care capacity, and availability of novel agents and HSCT hinder results in our region, reflecting barriers common to other LMICs. Recent developments in the diagnosis and treatment of this disease must be implemented through education, collaborative clinical research, and advocacy to improve outcomes.
Topics: Humans; Leukemia, Promyelocytic, Acute; Tretinoin; Latin America; Leukemia, Myeloid, Acute; Hematopoietic Stem Cell Transplantation; Antineoplastic Combined Chemotherapy Protocols
PubMed: 36607152
DOI: 10.1080/16078454.2022.2158015 -
Best Practice & Research. Clinical... Mar 2024The diversity of genetic and genomic abnormalities observed in acute myeloid leukemia (AML) reflects the complexity of these hematologic neoplasms. The detection of... (Review)
Review
The diversity of genetic and genomic abnormalities observed in acute myeloid leukemia (AML) reflects the complexity of these hematologic neoplasms. The detection of cytogenetic and molecular alterations is fundamental to diagnosis, risk stratification and treatment of AML. Chromosome rearrangements are well established in the diagnostic classification of AML, as are some gene mutations, in several international classification systems. Additionally, the detection of new mutational profiles at relapse and identification of mutations in the pre- and post-transplant settings are illuminating in understanding disease evolution and are relevant to the risk assessment of AML patients. In this review, we discuss recurrent cytogenetic abnormalities, as well as the detection of recurrent mutations, within the context of a normal karyotype, and in the setting of chromosome abnormalities. Two new classification schemes from the WHO and ICC are described, comparing these classifications in terms of diagnostic criteria and entity definition in AML. Finally, we discuss ways in which genomic sequencing can condense the detection of gene mutations and chromosome abnormalities into a single assay.
Topics: Humans; Leukemia, Myeloid, Acute; Chromosome Aberrations; Mutation; Genomics; Cytogenetic Analysis
PubMed: 38490763
DOI: 10.1016/j.beha.2023.101533 -
Blood Sep 2023
Topics: Humans; Leukemia, Myeloid, Acute; Tumor Suppressor Protein p53
PubMed: 37733379
DOI: 10.1182/blood.2023021386 -
Hematology. American Society of... Dec 2023Progression to myelodysplastic syndromes (MDS) and acute myeloid leukemia is one of the most serious complications of the inherited bone marrow failure and... (Review)
Review
Progression to myelodysplastic syndromes (MDS) and acute myeloid leukemia is one of the most serious complications of the inherited bone marrow failure and MDS-predisposition syndromes. Given the lack of predictive markers, this risk can also be a source of great uncertainty and anxiety to patients and their providers alike. Recent data show that some acquired mutations may provide a window into this risk. While maladaptive mechanisms, such as monosomy 7, are associated with a high risk of leukemogenesis, mutations that offset the inherited defect (known as somatic genetic rescue) may attenuate this risk. Somatic mutations that are shared with age-acquired clonal hematopoiesis mutations also show syndrome-specific patterns that may provide additional data as to disease risk. This review focuses on recent progress in this area with an emphasis on the biological underpinnings and interpretation of these patterns for patient care decisions.
Topics: Humans; Bone Marrow; Myelodysplastic Syndromes; Leukemia, Myeloid, Acute; Clonal Evolution; Mutation; Disease Progression
PubMed: 38066914
DOI: 10.1182/hematology.2023000469 -
Annals of Hematology Apr 2024Improved understanding of TP53 biology and the clinicopathological features of TP53-mutated myeloid neoplasms has led to the recognition of TP53-mutated acute myeloid... (Review)
Review
Improved understanding of TP53 biology and the clinicopathological features of TP53-mutated myeloid neoplasms has led to the recognition of TP53-mutated acute myeloid leukemia/myelodysplastic syndrome (TP53m AML/MDS) as a unique entity, characterized by dismal outcomes following conventional therapies. Several clinical trials have investigated combinations of emerging therapies for these patients with the poorest molecular prognosis among myeloid neoplasms. Although some emerging therapies have shown improvement in overall response rates, this has not translated into better overall survival, hence the notion that p53 remains an elusive target. New therapeutic strategies, including novel targeted therapies, immune checkpoint inhibitors, and monoclonal antibodies, represent a shift away from cytotoxic and hypomethylating-based therapies, towards approaches combining non-immune and novel immune therapeutic strategies. The triple combination of azacitidine and venetoclax with either magrolimab or eprenetapopt have demonstrated safety in early trials, with phase III trials currently underway, and promising interim clinical results. This review compiles background on TP53 biology, available and emerging therapies along with their mechanisms of action for the TP53m disease entity, current treatment challenges, and recently published data and status of ongoing clinical trials for TP53m AML/MDS.
Topics: Humans; Tumor Suppressor Protein p53; Azacitidine; Myelodysplastic Syndromes; Leukemia, Myeloid, Acute; Biology; Mutation
PubMed: 37770618
DOI: 10.1007/s00277-023-05462-5 -
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 -
Best Practice & Research. Clinical... Dec 2023Myeloid malignancies such as myelodysplastic syndrome (MDS) & acute myeloid leukemia (AML) are clonal diseases that emerge and progress due to the expansion of... (Review)
Review
Myeloid malignancies such as myelodysplastic syndrome (MDS) & acute myeloid leukemia (AML) are clonal diseases that emerge and progress due to the expansion of disease-initiating aberrant hematopoietic stem cells, that are not eliminated by conventional cytotoxic therapies. Hypomethylating agents(HMA), azacytidine and decitabine are the first line agents for treatment of MDS and a combination with BCL-2 inhibitor, venetoclax, is approved for AML induction in patients above 75 years and is also actively being investigated for use in high risk MDS. Resistance to these drugs has become a significant clinical challenge in treatment of myeloid malignancies. In this review, we discuss molecular mechanisms underlying the development of resistance to HMA and venetoclax. Insights into these mechanisms can help identify potential biomarkers for resistance prediction, aid in the development of combination therapies and strategies to prevent resistance and advance the field of cancer therapeutics.
Topics: Humans; Leukemia, Myeloid, Acute; Antineoplastic Agents; Bridged Bicyclo Compounds, Heterocyclic; Azacitidine; GATA2 Deficiency; Proto-Oncogene Proteins c-bcl-2
PubMed: 38092478
DOI: 10.1016/j.beha.2023.101521 -
Pathologie (Heidelberg, Germany) Dec 2023The World Health Organization classification (WHO-HAEM5) and the International Consensus Classification (ICC 2022) of myeloid neoplasms are based on the integration of... (Review)
Review
The World Health Organization classification (WHO-HAEM5) and the International Consensus Classification (ICC 2022) of myeloid neoplasms are based on the integration of clinical, morphologic, immunophenotypic, and genomic data. Flow cytometric immunophenotyping (FCIP) allows the identification, enumeration, and characterization of hematopoietic cells, and is therefore a powerful tool in the diagnosis, classification, and monitoring of hematological neoplasms. The vast majority of flow cytometry (FCM) studies in chronic myeloid neoplasms focus on its role in myelodysplastic neoplasms (MDS). FCM can also be helpful for the assessment of myeloproliferative neoplasms (MPN) and MDS/MPN, including the early detection of evolving myeloid or lymphoid blast crisis and the characterization of monocytic subsets. The classification of acute myeloid leukemia (AML) is primarily based on cytogenetic and molecular findings; however, FCIP is needed for subclassification of AML, not otherwise specified (NOS; ICC)/AML defined by differentiation (WHO-HAEM5). The main role of FCM in AML remains in making a rapid diagnosis and as a tool for measurable residual disease monitoring. Machine learning and artificial intelligence approaches can be used to analyze and classify FCM data. This article, based on an invited lecture at the 106th Annual Meeting of the German Society of Pathology in 2023, reviews the role of FCM in the classification of myeloid neoplasms, including recent publications on the application of artificial intelligence.
Topics: Humans; Flow Cytometry; Artificial Intelligence; Leukemia, Myeloid, Acute; Myeloproliferative Disorders; Myelodysplastic Syndromes
PubMed: 37991530
DOI: 10.1007/s00292-023-01272-8 -
International Journal of Hematology Dec 2023Myeloid sarcoma is a rare clinical entity that presents as an isolated proliferation of leukemic cells, concurrently with or at relapse of acute myeloid leukemia (AML),... (Review)
Review
Myeloid sarcoma is a rare clinical entity that presents as an isolated proliferation of leukemic cells, concurrently with or at relapse of acute myeloid leukemia (AML), myelodysplastic syndromes/neoplasms (MDS), chronic myeloid leukemia (CML), and myeloproliferative neoplasm (MPN). Myeloid sarcoma disrupts the normal architecture of its surrounding tissues. When it forms in long bones, it can cause their pathological fracture. We recently experienced a rare case of MDS presenting with myeloid sarcoma in the femur that eventually resulted in its pathological fracture. Detailed chromosomal analysis of the bone marrow cells suggested emergence of myeloid sarcoma during the fast-paced progression of MDS just after acquiring trisomy 22. A comprehensive review of previous cases of myeloid sarcoma-associated pathological fracture indicated possible involvement of structural rearrangements of chromosomes 9 and 22. Management of myeloid sarcoma should continue to improve, and clinicians should note that myeloid sarcoma with specific chromosomal alterations needs extra medical attention to prevent pathological fracture.
Topics: Humans; Sarcoma, Myeloid; Fractures, Spontaneous; Myeloproliferative Disorders; Myelodysplastic Syndromes; Leukemia, Myeloid, Acute
PubMed: 37707761
DOI: 10.1007/s12185-023-03656-1 -
Frontiers in Immunology 2024The interplay between myeloid cells and T-lymphocytes is critical to the regulation of host defense and inflammation resolution. Dysregulation of this interaction can... (Review)
Review
The interplay between myeloid cells and T-lymphocytes is critical to the regulation of host defense and inflammation resolution. Dysregulation of this interaction can contribute to the development of chronic inflammatory diseases. Important among these diseases is atherosclerosis, which refers to focal lesions in the arterial intima driven by elevated apolipoprotein B-containing lipoproteins, notably low-density lipoprotein (LDL), and characterized by the formation of a plaque composed of inflammatory immune cells, a collection of dead cells and lipids called the necrotic core, and a fibrous cap. As the disease progresses, the necrotic core expands, and the fibrous cap becomes thin, which increases the risk of plaque rupture or erosion. Plaque rupture leads to a rapid thrombotic response that can give rise to heart attack, stroke, or sudden death. With marked lowering of circulating LDL, however, plaques become more stable and cardiac risk is lowered-a process known as atherosclerosis regression. A critical aspect of both atherosclerosis progression and regression is the crosstalk between innate (myeloid cells) and adaptive (T-lymphocytes) immune cells. Myeloid cells are specialized at clearing apoptotic cells by a process called efferocytosis, which is necessary for inflammation resolution. In advanced disease, efferocytosis is impaired, leading to secondary necrosis of apoptotic cells, inflammation, and, most importantly, defective tissue resolution. In regression, efferocytosis is reawakened aiding in inflammation resolution and plaque stabilization. Here, we will explore how efferocytosing myeloid cells could affect T-cell function and vice versa through antigen presentation, secreted factors, and cell-cell contacts and how this cellular crosstalk may contribute to the progression or regression of atherosclerosis.
Topics: Humans; Atherosclerosis; T-Lymphocytes; Myeloid Cells; Animals; Cell Communication; Phagocytosis; Apoptosis; Plaque, Atherosclerotic
PubMed: 38873597
DOI: 10.3389/fimmu.2024.1403150