-
Molecular Genetics and Metabolism Aug 2020Acute myeloid leukemia (AML) is a complex, heterogenous hematological malignancy caused by mutations in myeloid differentiation and proliferation. Response to therapy... (Review)
Review
Acute myeloid leukemia (AML) is a complex, heterogenous hematological malignancy caused by mutations in myeloid differentiation and proliferation. Response to therapy and long-term outcomes vary widely based on chromosomal and molecular aberrations. Many platforms have been used to characterize and stratify AML. Metabolomics, the global profiling of small molecules in a biological sample, has emerged in the last decade as an important tool for studying the metabolic dependency of cancer cells. Metabolic reprogramming is not only an important manifestation of AML but clinically relevant for diagnosis, risk stratification and targeted drug development. In this review, we discuss notable metabolic studies of the last decade and their application to novel therapies.
Topics: Animals; Biomarkers, Tumor; Humans; Leukemia, Myeloid, Acute; Metabolome
PubMed: 32457018
DOI: 10.1016/j.ymgme.2020.05.005 -
Seminars in Diagnostic Pathology Nov 2020Myeloid diseases detected as primary or secondary lesions in the lung and pleura are rare. Clinical presentations and radiographic results may vary significantly... (Review)
Review
Myeloid diseases detected as primary or secondary lesions in the lung and pleura are rare. Clinical presentations and radiographic results may vary significantly depending on the nature of the diseases. The most common diseases associated with lung and pleura involvement are myeloid sarcoma/acute myeloid leukemia (AML) and extramedullary hematopoiesis (EMH). AML typically represents localized involvement by systemic acute leukemia, while EMH is frequently secondary to underlying benign hematolymphoid disorders or myeloproliferative neoplasms. This review provides an overview of the pathogenesis, clinical presentations, radiologic/imaging studies, pathologic and genetic findings, and treatment/outcomes associated with myeloid diseases in the lung and pleura.
Topics: Diagnosis, Differential; Genetic Predisposition to Disease; Hematopoiesis, Extramedullary; Humans; Leukemia, Myeloid, Acute; Lung; Myeloproliferative Disorders; Pathology, Molecular; Pleura; Sarcoma, Myeloid; Thalassemia; Treatment Outcome
PubMed: 32591154
DOI: 10.1053/j.semdp.2020.06.002 -
Palliative & Supportive Care Feb 2021
Topics: Humans; Leukemia, Myeloid, Acute; Patient Acceptance of Health Care
PubMed: 32662378
DOI: 10.1017/S147895152000053X -
Current Hematologic Malignancy Reports Aug 2020Nucleophosmin (NPM1) mutations are encountered in myeloid neoplasia and are present in ~ 30% of de novo acute myeloid leukemia cases. This review summarizes features... (Review)
Review
PURPOSE OF REVIEW
Nucleophosmin (NPM1) mutations are encountered in myeloid neoplasia and are present in ~ 30% of de novo acute myeloid leukemia cases. This review summarizes features of mutant NPM1-related disease, with a particular emphasis on recent discoveries relevant to disease monitoring, prognostication, and therapeutic intervention.
RECENT FINDINGS
Recent studies have shown that HOX/MEIS gene overexpression is central to the survival of NPM1-mutated cells. Two distinct classes of small molecule drugs, BH3 mimetics and menin-MLL interaction inhibitors, have demonstrated exquisite leukemic cell toxicity in preclinical AML models associated with HOX/MEIS overexpression, and the former of these has shown efficacy in older treatment-naïve NPM1-mutated AML patients. The results of ongoing clinical trials further investigating these compounds will be of particular importance and may alter the clinical management of patients with NPM1-mutated myeloid neoplasms. Significant scientific advancements over the last decade, including improved sequencing and disease monitoring techniques, have fostered a much deeper understanding of mutant NPM1 disease biology, prognostication, and opportunities for therapeutic intervention. These discoveries have led to the development of clinical assays that permit the detection and monitoring of mutant NPM1 and have paved the way for future investigation of targeted therapeutics using emerging cutting-edge techniques.
Topics: Animals; Genetic Predisposition to Disease; Humans; Leukemia, Myeloid, Acute; Mutation; Myelodysplastic Syndromes; Neoplasm, Residual; Nuclear Proteins; Nucleophosmin; Phenotype; Prognosis; Risk Factors
PubMed: 32494951
DOI: 10.1007/s11899-020-00592-3 -
Journal of Clinical Oncology : Official... Mar 2020
Topics: Culturally Competent Care; Cyprus; England; Humans; Leukemia, Myeloid, Acute; Male; Narration
PubMed: 31855507
DOI: 10.1200/JCO.19.02828 -
Blood Jan 2023
Topics: Humans; Aged; Aminopyridines; Triazines; Leukemia, Myeloid, Acute
PubMed: 36633887
DOI: 10.1182/blood.2022016946 -
Current Hematologic Malignancy Reports Oct 2023CCAAT enhancer binding protein A (CEBPA) gene mutation is one of the common genetic alterations in acute myeloid leukemia (AML), which can be associated with sporadic... (Review)
Review
PURPOSE OF REVIEW
CCAAT enhancer binding protein A (CEBPA) gene mutation is one of the common genetic alterations in acute myeloid leukemia (AML), which can be associated with sporadic and familial AML.
RECENT FINDINGS
Due to the recent advances in molecular testing and the prognostic role of CEBPA mutation in AML, the definition for AML with CEBPA mutation (AML-CEBPA) has significantly changed. This review provides the rationale for the updates on classifications, and the impacts on laboratory evaluation and clinical management for sporadic and familial AML-CEBPA patients. In addition, minimal residual disease assessment post therapy to stratify disease risk and stem cell transplant in selected AML-CEBPA patients are discussed. Taken together, the recent progresses have shifted the definition, identification, and management of patients with AML-CEBPA.
Topics: Humans; Leukemia, Myeloid, Acute; Mutation; CCAAT-Enhancer-Binding Proteins; Prognosis
PubMed: 37261703
DOI: 10.1007/s11899-023-00699-3 -
Blood Jul 2023
Topics: Humans; Leukemia, Myeloid, Acute; Genomics
PubMed: 37410505
DOI: 10.1182/blood.2023020672 -
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 -
Annals of Hematology Mar 2020MicroRNAs are a class of small non-coding RNAs that are 19-22 nucleotides in length and regulate a variety of biological processes at the post-transcriptional level.... (Review)
Review
MicroRNAs are a class of small non-coding RNAs that are 19-22 nucleotides in length and regulate a variety of biological processes at the post-transcriptional level. MicroRNA dysregulation disrupts normal biological processes, resulting in tumorigenesis. Acute myeloid leukemia is an invasive hematological malignancy characterized by the abnormal proliferation and differentiation of immature myeloid cells. Due to the low 5-year survival rate, there is an urgent need to discover novel diagnostic markers and therapeutic targets. In recent years, microRNAs have been shown to play important roles in hematological malignancies by acting as tumor suppressors and oncogenes. MicroRNAs have the potential to be a breakthrough in the diagnosis and treatment of acute myeloid leukemia. In this review, we summarize the biology of microRNAs and discuss the relationships between microRNA dysregulation and acute myeloid leukemia in the following aspects: signaling pathways, the abnormal biological behavior of acute myeloid leukemia cells, the clinical application of microRNAs and competing endogenous RNA regulatory networks.
Topics: Carcinogenesis; Cell Differentiation; Gene Expression Regulation, Leukemic; Hematologic Neoplasms; Humans; Leukemia, Myeloid, Acute; MicroRNAs; RNA, Neoplasm; Signal Transduction
PubMed: 31932900
DOI: 10.1007/s00277-019-03887-5