Biological and pathogenic roles of major genes harbored in intrachromosomal amplification of chromosome 21 in childhood acute lymphoblastic leukemia (Review).

Chromosomal alterations are key in the study of acute lymphoblastic leukemia (ALL) as they facilitate the establishment of risks, prognosis and treatment. The intrachromosomal amplification of chromosome 21 (iAMP21) can generate a structurally heterogeneous derivative chromosome 21 that can typically replace a normal chromosome 21 and defines a subtype of high-risk childhood ALL (iAMP21-ALL). A region commonly involved in this amplification has been delineated and includes genes such as chromatin assembly factor 1 subunit B, dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A, erythroblast transformation-specific-related gene, high mobility group nucleosome binding domain 1 and Runt-related transcription factor 1, but its role in the development of leukemia has not yet been fully elucidated. The Down syndrome critical region on chromosome 21 (ripply transcriptional repressor 3) overlaps with a common amplification region in iAMP21. Therefore, it has been hypothesized that iAMP21-related genes may be associated with Down syndrome susceptibility to ALL. The present review described the biological role of iAMP21-related genes and their relationship with ALL development.