Natural history of acute lymphoblastic leukemia in neurofibromatosis type 1 monozygotic twins

Although the natural history of acute lymphoblastic leukemia (ALL) is clinically silent, identical twin pairs suffering from concordant leukemia provide a unique and tractable model to better understand the clonal evolution of this disease.1 Recently, genetic studies on ALL have revealed not a linear sequence of mutation acquisition but rather a clonal development model based on complex branching similar to Darwin’s evolution trees and natural selection. Indeed, a frequently occurring prenatal first hit is followed by the acquisition of critical and secondary copy number alterations (CNAs) in different subclones, which gain a selective advantage giving rise to leukemia.