Familial myelodysplastic syndrome/acute leukemia syndromes: a review and utility for translational investigations.
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.
Department of Medicine, The University of Chicago, Chicago, Illinois.
Allison H
AH
West
Lucy A
LA
Godley
Jane E
JE
Churpek
D020022:Genetic Predisposition to Disease; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy*; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy*; D057170:Translational Research, Biomedical
CEBPA; GATA2; RUNX1; familial; leukemia; myelodysplastic syndrome