Clonal Architecture and Evolutionary Dynamics in Acute Myeloid Leukemias
Génomes, Biologie Cellulaire et Thérapeutique U944, INSERM, CNRS, Université de Paris, 75010 Paris, France
Laboratoire d’Hématologie, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, 75010 Paris, France
Institut d’Histoire et Philosophie des Sciences et des Techniques UMR 8590, CNRS, Université Paris 1 Panthéon-Sorbonne, 75010 Paris, France
Gustave Roussy Cancer Center, UMR1287, 94805 Villejuif, France
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
Received: 27 August 2021
Revised: 27 September 2021
Accepted: 28 September 2021
Published: 29 September 2021
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.