Clonal Architecture and Evolutionary Dynamics in Acute Myeloid Leukemias

Area of Science:

• Hematology
• Cancer Biology
• Evolutionary Medicine

Background:

• Acute myeloid leukemia (AML) is driven by accumulating genetic and epigenetic alterations within an aging hematopoietic system.
• Intratumoral diversity of leukemic cells has been illuminated by advances in high-throughput sequencing and single-cell technologies.
• Understanding leukemic cell heterogeneity is crucial for defining the concept of a leukemic clone beyond genetics.

Purpose of the Study:

• To review sources of genetic, epigenetic, and functional heterogeneity in leukemic cells.
• To discuss clonal diversity in AML, considering richness and evenness.
• To explore mechanisms of clonal emergence and dynamics, including influences on clonal fitness.

Main Methods:

• Review of current literature on genetic, epigenetic, and functional heterogeneity in AML.
• Analysis of clonal diversity dimensions: richness and evenness.
• Discussion of factors influencing clonal emergence and dynamics, such as mutation rates, cell population size, and evolutionary forces.

Main Results:

• Leukemic cell heterogeneity arises from multiple genetic, epigenetic, and functional sources.
• Clonal diversity in AML can be quantified by richness and evenness.
• Mechanisms driving clonal emergence and dynamics involve mutation rates, population size, neutral drift, and cell-intrinsic/extrinsic factors.

Conclusions:

• AML heterogeneity is a complex evolutionary process.
• Genetic and epigenetic diversity of leukemic cells impacts patient prognosis.
• A deeper understanding of AML evolution can inform novel therapeutic strategies.