In:
Cancer Science, Wiley, Vol. 110, No. 10 ( 2019-10), p. 3358-3367
Abstract:
Children with Down syndrome ( DS ) are at a 20‐fold increased risk for acute lymphoblastic leukemia ( ALL ). Compared to children with ALL and no DS (non‐ DS ‐ ALL ), those with DS and ALL ( DS ‐ ALL ) harbor uncommon genetic alterations, suggesting DS ‐ ALL could have distinct biological features. Recent studies have implicated several genes on chromosome 21 in DS ‐ ALL , but the precise mechanisms predisposing children with DS to ALL remain unknown. Our integrated genetic/epigenetic analysis revealed that DS ‐ ALL was highly heterogeneous with many subtypes. Although each subtype had genetic/epigenetic profiles similar to those found in non‐ DS ‐ ALL , the subtype distribution differed significantly between groups. The Philadelphia chromosome‐like subtype, a high‐risk B‐cell lineage variant relatively rare among the entire pediatric ALL population, was the most common form in DS ‐ ALL . Hypermethylation of RUNX 1 on chromosome 21 was also found in DS ‐ ALL , but not non‐ DS ‐ ALL . RUNX 1 is essential for differentiation of blood cells, especially B cells; thus, hypermethylation of the RUNX 1 promoter in B‐cell precursors might be associated with increased incidence of B‐cell precursor ALL in DS patients.
Type of Medium:
Online Resource
ISSN:
1347-9032
,
1349-7006
Language:
English
Publisher:
Wiley
Publication Date:
2019
detail.hit.zdb_id:
2115647-5
detail.hit.zdb_id:
2111204-6
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