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Modern Pathology : An Official Journal... Feb 2024In this manuscript, we review myeloid neoplasms in the fifth edition of the World Health Organization classification of hematolymphoid tumors (WHO-HEM5), focusing on... (Review)
Review
In this manuscript, we review myeloid neoplasms in the fifth edition of the World Health Organization classification of hematolymphoid tumors (WHO-HEM5), focusing on changes from the revised fourth edition (WHO-HEM4R). Disease types and subtypes have expanded compared with WHO-HEM4R, mainly because of the expansion in genomic knowledge of these diseases. The revised classification is based on a multidisciplinary approach including input from a large body of pathologists, clinicians, and geneticists. The revised classification follows a hierarchical structure allowing usage of family (class)-level definitions where the defining diagnostic criteria are partially met or a complete investigational workup has not been possible. Overall, the WHO-HEM5 revisions to the classification of myeloid neoplasms include major updates and revisions with increased emphasis on genetic and molecular drivers of disease. The most notable changes have been applied to the sections of acute myeloid leukemia and myelodysplastic neoplasms (previously referred to as myelodysplastic syndrome) with incorporation of novel, disease-defining genetic changes. In this review we focus on highlighting the updates in the classification of myeloid neoplasms, providing a comparison with WHO-HEM4R, and offering guidance on how the new classification can be applied to the diagnosis of myeloid neoplasms in routine practice.
Topics: Humans; Myeloproliferative Disorders; Myelodysplastic Syndromes; Leukemia, Myeloid, Acute; World Health Organization; Hematologic Neoplasms
PubMed: 38043791
DOI: 10.1016/j.modpat.2023.100397 -
Biomedicine & Pharmacotherapy =... Dec 2023Venetoclax is a potent inhibitor that specifically targets B-cell lymphoma-2 (BCL-2), which has been demonstrated to be effective in preclinical studies utilizing acute... (Review)
Review
Venetoclax is a potent inhibitor that specifically targets B-cell lymphoma-2 (BCL-2), which has been demonstrated to be effective in preclinical studies utilizing acute myeloid leukemia (AML) cell lines and xenograft models. Significant antileukemic activity was also observed in clinical trials, both as a monotherapy and in combination with other drugs. This novel therapeutic approach has revolutionized the treatment prospects for AML patients with unfavorable prognoses and those who are unable to tolerate intensive chemotherapy. Nevertheless, further investigations are required to establish the optimal dosing, sequencing, and combinational strategies of venetoclax for AML treatments. Additionally, identifying biomarkers is crucial for predicting response and resistance to this targeted intervention. In this review, we provide an overview of venetoclax-based therapy for AML and explore potential avenues for future research.
Topics: Humans; Adult; Proto-Oncogene Proteins c-bcl-2; Apoptosis; Leukemia, Myeloid, Acute; Bridged Bicyclo Compounds, Heterocyclic
PubMed: 37925935
DOI: 10.1016/j.biopha.2023.115820 -
Trends in Cancer Sep 2023Myeloid malignancies, a group of hematopoietic disorders that includes acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), and myeloproliferative neoplasms... (Review)
Review
Myeloid malignancies, a group of hematopoietic disorders that includes acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), and myeloproliferative neoplasms (MPNs), are caused by the accumulation of genetic and epigenetic changes in hematopoietic stem and progenitor cells (HSPCs) over time. Despite the relatively low number of genomic drivers compared with other forms of cancer, the process by which these changes shape the genomic architecture of myeloid malignancies remains elusive. Recent advancements in clonal hematopoiesis research and the use of cutting-edge single cell technologies have shed new light on the developmental process of myeloid malignancies. In this review, we delve into the intricacies of clonal evolution in myeloid malignancies and its implications for the development of new diagnostic and therapeutic approaches.
Topics: Humans; Myelodysplastic Syndromes; Leukemia, Myeloid, Acute; Hematopoietic Stem Cells; Epigenesis, Genetic; Clonal Evolution
PubMed: 37302922
DOI: 10.1016/j.trecan.2023.05.004 -
Leukemia & Lymphoma 2023Advances in the treatment of acute myeloid leukemia (AML) over the last 40 years have been limited. With an improved understanding of the pathophysiology of the... (Review)
Review
Advances in the treatment of acute myeloid leukemia (AML) over the last 40 years have been limited. With an improved understanding of the pathophysiology of the disease, the advent of new treatment options has enriched the armamentarium of the physician to combat the disease. Mutations of the isocitrate dehydrogenase (s) genes are common in AML and occur in 20-30% of cases. These mutations lead to DNA hypermethylation, aberrant gene expression, cell proliferation, and abnormal differentiation. Targeting mutant , either as monotherapy or in combination with hypomethylating agents (HMAs) or BCL-2 inhibitors, has opened new avenues of therapy for these patients.This review will outline the function of s and focus on the biological effects of mutations in AML, their prognosis and treatment options.
Topics: Humans; Aminopyridines; Antineoplastic Agents; Isocitrate Dehydrogenase; Leukemia, Myeloid, Acute; Mutation; Triazines
PubMed: 37462435
DOI: 10.1080/10428194.2023.2237153 -
Blood Sep 2023
Topics: Humans; Myeloid Differentiation Factor 88; Signal Transduction; Adaptor Proteins, Signal Transducing; Leukemia, Myeloid, Acute; Neoplasms, Second Primary; Interleukin-1 Receptor-Associated Kinases
PubMed: 37707874
DOI: 10.1182/blood.2023020812 -
Blood Jul 2023
Topics: Humans; Oxidative Phosphorylation; Mitochondria; Cell Line, Tumor; Leukemia, Myeloid, Acute
PubMed: 37498585
DOI: 10.1182/blood.2023021129 -
Blood Dec 2023
Topics: Humans; Histones; Methylation; Nucleotidyltransferases; Immunity; Leukemia, Myeloid, Acute; Tumor Suppressor Protein p53; Protein Serine-Threonine Kinases
PubMed: 38060272
DOI: 10.1182/blood.2023021950 -
Haematologica Dec 2023
Topics: Humans; CD47 Antigen; Leukemia, Myeloid, Acute; Antibodies, Monoclonal; Genotype
PubMed: 37381766
DOI: 10.3324/haematol.2023.283154 -
Best Practice & Research. Clinical... Dec 2023According to the 2022 World Health Organization (WHO) Classification (5th edition), the term myelodysplastic neoplasms (abbreviated MDS) has been introduced to replace... (Review)
Review
According to the 2022 World Health Organization (WHO) Classification (5th edition), the term myelodysplastic neoplasms (abbreviated MDS) has been introduced to replace myelodysplastic syndromes. MDS are a group of clonal hematopoietic stem cell diseases characterized by cytopenia(s), dysplasia in one or more of lineages, ineffective hematopoiesis, and an increased risk of progression to bone marrow failure or to acute myeloid leukemia (AML). Current NCCN guidelines and recent review articles have provided in depth discussion on the clinical diagnosis and management of MDS. This review will focus on discussion of the WHO and International Consensus Classification (ICC) updates on the role of cytogenetics and molecular genetics in the diagnosis and risk stratification of MDS.
Topics: Humans; Myelodysplastic Syndromes; Leukemia, Myeloid, Acute; Prognosis; Molecular Biology; Cytogenetic Analysis
PubMed: 38092472
DOI: 10.1016/j.beha.2023.101512 -
Haematologica Oct 2023
Menin inhibitor ziftomenib (KO-539) synergizes with drugs targeting chromatin regulation or apoptosis and sensitizes acute myeloid leukemia with rearrangement or mutation to venetoclax.
Topics: Humans; Chromatin; Leukemia, Myeloid, Acute; Myeloid-Lymphoid Leukemia Protein; Nuclear Proteins; Mutation; Apoptosis
PubMed: 37102614
DOI: 10.3324/haematol.2022.282160