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Genomic landscape and clonal evolution of AML

Item Type:Book Section
Title:Genomic landscape and clonal evolution of AML
Creators Name:Noerenberg, D., Damm, F. and Bullinger, L.
Abstract:In most cases, acute myeloid leukemia (AML) develops from hematopoietic cells that have acquired somatic mutations over time. Since the first balanced translocation described by Janet Rowley in 1972, there has been a growing knowledge on the pathogenic relevance of the genomic aberrations underlying the biological and clinical complexity of AML. Recently, molecular genomics have begun to unravel mechanisms of clonal leukemia evolution and disease dynamics, especially as novel technologies allow us to capture multiple competing clones coexisting at any disease time point. In this book chapter, a short summary of the genomic landscape and the impact of genomic changes on the individual patient outcome are given. Molecular diagnostics provide the basis for clinically relevant genomic classification schemes such as the 2017 European LeukemiaNet (ELN) guidelines. Next to the well-established cytogenetic subgroups and molecular markers such as NPM1, CEBPA, and FLT3, also the screening for RUNX1, TP53, and ASXL1 mutations is now recommended. In the future, a better understanding of the clonal evolution leading to malignant transformation and selection of resistant leukemia clones will not only be crucial for refined determination of measurable residual disease (MRD), but will also result in improved guidance of targeted therapeutic strategies.
Keywords:Acute Myeloid Leukemia (AML), Genomic Landscape, Clonal Evolution, Driver Mutations, Leukemia Stem Cells, Molecular Diagnostics, Next-Generation Sequencing (NGS), "Clonal Hematopoiesis Of Indeterminate Potential" (CHIP), Measurable Residual Disease (MRD), Targeted Therapy
Source:Acute Myeloid Leukemia
Series Name:Hematologic Malignancies
Title of Book:Acute Myeloid Leukemia
ISSN:2197-9766
ISBN:978-3-030-72675-1
Publisher:Springer
Page Range:103-118
Date:2021
Official Publication:https://doi.org/10.1007/978-3-030-72676-8_5

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