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Familial myelodysplastic syndrome/acute leukemia syndromes: a review and utility for translational investigations
Author(s) -
West Allison H.,
Godley Lucy A.,
Churpek Jane E.
Publication year - 2014
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/nyas.12346
Subject(s) - myelodysplastic syndromes , myeloid leukemia , medicine , cebpa , genetic testing , leukemia , mutation , genetics , immunology , biology , gene , bone marrow
The familial myelodysplastic (MDS)/acute leukemia (AL) predisposition syndromes are inherited disorders that lead to significantly increased lifetime risks of MDS and AL development. At present, four recognized syndromes have Clinical Laboratory Improvement Amendments—certified testing for their respective germ‐line mutations: telomere biology disorders due to mutation of TERC or TERT , familial acute myeloid leukemia (AML) with mutated CEBPA , familial MDS/AML with mutated GATA2 , and familial platelet disorder with propensity to myeloid malignancy. These disorders are heterogeneous with regard to their causative genetic mutations, clinical presentation, and progression to MDS/AL. However, as a group, they all share the unique requirement for a high index of clinical suspicion to allow appropriate genetic counseling, genetic testing, and mutation‐specific clinical management. In addition, translational investigations of individuals and families with these syndromes provide a rare opportunity to understand key pathways underlying susceptibility and progression to MDS/AL and allow the possibility of novel strategies for the prevention and treatment of both familial and sporadic forms of MDS/AL.