Genetic Mutation

Genetic mutation plays a pivotal role in the etiology of ALL in children born with Down syndrome with the associated trisomy 21 chromosome abnormality.

Alteration and activation of the GATA-1 hematopoietic transcription factor increases the risk for development of ALL and increases the incidence of acute megakaryocytic leukemia as well.31-35 That hematologic malignancies representing different cell lines may become malignant suggests that multiple signaling pathways may be affected by this and other chromosome abnormalities.36 Of interest, the more detrimental chromosome abnormalities, t(9;22) and t(4;11), occur infrequently in Down syndrome.33-35 Favorable abnormalities of the TEL/AML1 fusion, denoted by the t(12;21) translocation, are also less frequent in Down syndrome.

ALL may also arise in the setting of the Li-Fraumeni syndrome, with associated abnormalities of p53, Bloom syndrome, and others predisposing to ALL and to multiple other cancers.36

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