Molecular alterations governing predisposition to myelodysplastic syndromes: Insights from Shwachman-Diamond syndrome.

Identifying germline mutations responsible for genetic predisposition to myeloid malignancies would be useful in creating opportunities for early intervention. Recent genomic and functional studies in Shwachman-Diamond syndrome (SDS) have deciphered distinct roles for heterozygous mutations in EIF6 and TP53 in alleviating germline genetic stress and a role for biallelic TP53 mutations in malignant progression. This review has summarized evidence for a mechanistic framework underlying SDS that can potentially be applied to the study of other germline myelodysplastic syndromes (MDS) predisposition disorders.