Genetic susceptibility to acute lymphoblastic leukemia pre- and post genome-wide association studies era

Abstract

Analysis of genetic predisposition in pathogenesis of acute lymphoblastic leukemia (ALL) is
very difficult because of very low rate of morbidity in general population. Candidate gene
approaches have revealed many loci associated with ALL e.g. genes encoding proteins taking
part in carcinogen metabolism or DNA repairing pathways. Results of these studies often were
not replicated in other populations. The breakthrough took place at the moment of introduction
of genome-wide association studies, which allow to analyze 500 000–2 000 000 polymorphic
sites in population exceeding 1000 people. This method contributed to identification of new
regions in the genome, that are related to ALL pathogenesis and results of these studies were confirmed in other populations. Interestingly, the most of these genes (IKZF1, ARID5B,
CEBPE) are involved in the regulation of lymphocytes differentiation which sheds a new light
on unknown aspects of pathogenesis of ALL in children. It seems that in ALL may occur as
a result of genetically determined disturbance of lymphocytes differentiation or/and inherited
immunological dysfunctions leading to inefficient elimination of leukemic clones.