Understanding the origin and role of driver mutations in the case of Acute Myeloid Leukemia using a simulation study

Abstract

Cancer is a leading cause of death worldwide, with millions of new cases diagnosed each year. Understanding how those cancers arise within individuals is a major challenge. Here we focus on Acute Myeloid Leukemia (AML) a type of blood cancer in the bone marrow that involves the formation of abnormal myeloid cells in an individual. Each year, 190,000 cases are diagnosed worldwide, of which 147,000 die.  (Acute Myeloid Leukemia, n.d.)

In this paper, we aim to better understand the origin of AML and the role of driver mutations at the individual level.

We build a Birth-Death model to explore the role of mutation along with cell birth rate, cell death rate, and tissue size. Each simulation is individual-specific, which allows us to consider stochasticity across individuals.

We show that initial cell birth rate and cell death rate only play a minor role in cancer progression, even if there is a large inter-individual variance. On the contrary, we show that driver mutation rates play a more critical role in causing Acute Myeloid Leukemia. All in all, our paper highlights large variability in cancer progression across individuals and the major role of driver mutations in causing AML. This simulation model could be used to study other types of cancers.