Cargando…
Clonal Architecture and Evolutionary Dynamics in Acute Myeloid Leukemias
SIMPLE SUMMARY: 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 intratumor...
Autores principales: | , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8507870/ https://www.ncbi.nlm.nih.gov/pubmed/34638371 http://dx.doi.org/10.3390/cancers13194887 |
_version_ | 1784581962042703872 |
---|---|
author | Duchmann, Matthieu Laplane, Lucie Itzykson, Raphael |
author_facet | Duchmann, Matthieu Laplane, Lucie Itzykson, Raphael |
author_sort | Duchmann, Matthieu |
collection | PubMed |
description | SIMPLE SUMMARY: 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. ABSTRACT: 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. |
format | Online Article Text |
id | pubmed-8507870 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-85078702021-10-13 Clonal Architecture and Evolutionary Dynamics in Acute Myeloid Leukemias Duchmann, Matthieu Laplane, Lucie Itzykson, Raphael Cancers (Basel) Review SIMPLE SUMMARY: 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. ABSTRACT: 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. MDPI 2021-09-29 /pmc/articles/PMC8507870/ /pubmed/34638371 http://dx.doi.org/10.3390/cancers13194887 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Duchmann, Matthieu Laplane, Lucie Itzykson, Raphael Clonal Architecture and Evolutionary Dynamics in Acute Myeloid Leukemias |
title | Clonal Architecture and Evolutionary Dynamics in Acute Myeloid Leukemias |
title_full | Clonal Architecture and Evolutionary Dynamics in Acute Myeloid Leukemias |
title_fullStr | Clonal Architecture and Evolutionary Dynamics in Acute Myeloid Leukemias |
title_full_unstemmed | Clonal Architecture and Evolutionary Dynamics in Acute Myeloid Leukemias |
title_short | Clonal Architecture and Evolutionary Dynamics in Acute Myeloid Leukemias |
title_sort | clonal architecture and evolutionary dynamics in acute myeloid leukemias |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8507870/ https://www.ncbi.nlm.nih.gov/pubmed/34638371 http://dx.doi.org/10.3390/cancers13194887 |
work_keys_str_mv | AT duchmannmatthieu clonalarchitectureandevolutionarydynamicsinacutemyeloidleukemias AT laplanelucie clonalarchitectureandevolutionarydynamicsinacutemyeloidleukemias AT itzyksonraphael clonalarchitectureandevolutionarydynamicsinacutemyeloidleukemias |