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Review

Clonal Architecture and Evolutionary Dynamics in Acute Myeloid Leukemias

1
Génomes, Biologie Cellulaire et Thérapeutique U944, INSERM, CNRS, Université de Paris, 75010 Paris, France
2
Laboratoire d’Hématologie, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, 75010 Paris, France
3
Institut d’Histoire et Philosophie des Sciences et des Techniques UMR 8590, CNRS, Université Paris 1 Panthéon-Sorbonne, 75010 Paris, France
4
Gustave Roussy Cancer Center, UMR1287, 94805 Villejuif, France
5
Département Hématologie et Immunologie, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, 75010 Paris, France
*
Author to whom correspondence should be addressed.
Academic Editors: Frederik Damm and Lars B. Bullinger
Cancers 2021, 13(19), 4887; https://doi.org/10.3390/cancers13194887
Received: 27 August 2021 / Revised: 27 September 2021 / Accepted: 28 September 2021 / Published: 29 September 2021
(This article belongs to the Special Issue Genetic Findings in Acute Myeloid Leukemia)
Acute myeloid leukemias (AML) results from the accumulation of genetic and epigenetic alterations, often in the context of an aging hematopoietic environment. The development of high-throughput sequencing—and more recently, of single-cell technologies—has shed light on the intratumoral diversity of leukemic cells. Taking AML as a model disease, we review the multiple sources of heterogeneity of leukemic cells and discuss the definition of a leukemic clone. After introducing the two dimensions contributing to clonal diversity, namely, richness (number of leukemic clones) and evenness (distribution of clone sizes), we discuss the mechanisms at the origin of clonal emergence and the causes of clonal dynamics including neutral drift, and cell-intrinsic and -extrinsic influences on clonal fitness. After reviewing the prognostic role of leukemic diversity on patients’ outcome, we discuss how a better understanding of AML as an evolutionary process could lead to the design of novel therapeutic strategies for this disease.
Acute myeloid leukemias (AML) results from the accumulation of genetic and epigenetic alterations, often in the context of an aging hematopoietic environment. The development of high-throughput sequencing—and more recently, of single-cell technologies—has shed light on the intratumoral diversity of leukemic cells. Taking AML as a model disease, we review the multiple sources of genetic, epigenetic, and functional heterogeneity of leukemic cells and discuss the definition of a leukemic clone extending its definition beyond genetics. After introducing the two dimensions contributing to clonal diversity, namely, richness (number of leukemic clones) and evenness (distribution of clone sizes), we discuss the mechanisms at the origin of clonal emergence (mutation rate, number of generations, and effective size of the leukemic population) and the causes of clonal dynamics. We discuss the possible role of neutral drift, but also of cell-intrinsic and -extrinsic influences on clonal fitness. After reviewing available data on the prognostic role of genetic and epigenetic diversity of leukemic cells on patients’ outcome, we discuss how a better understanding of AML as an evolutionary process could lead to the design of novel therapeutic strategies in this disease. View Full-Text
Keywords: acute myeloid leukemia; clonal heterogeneity; evolutionary dynamics; drug resistance; prognosis acute myeloid leukemia; clonal heterogeneity; evolutionary dynamics; drug resistance; prognosis
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MDPI and ACS Style

Duchmann, M.; Laplane, L.; Itzykson, R. Clonal Architecture and Evolutionary Dynamics in Acute Myeloid Leukemias. Cancers 2021, 13, 4887. https://doi.org/10.3390/cancers13194887

AMA Style

Duchmann M, Laplane L, Itzykson R. Clonal Architecture and Evolutionary Dynamics in Acute Myeloid Leukemias. Cancers. 2021; 13(19):4887. https://doi.org/10.3390/cancers13194887

Chicago/Turabian Style

Duchmann, Matthieu, Lucie Laplane, and Raphael Itzykson. 2021. "Clonal Architecture and Evolutionary Dynamics in Acute Myeloid Leukemias" Cancers 13, no. 19: 4887. https://doi.org/10.3390/cancers13194887

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