Familial myelodysplastic syndrome/acute leukemia syndromes: a review and utility for translational investigations

Ann N Y Acad Sci. 2014 Mar;1310(1):111-8. doi: 10.1111/nyas.12346. Epub 2014 Jan 27.


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.

Keywords: CEBPA; GATA2; RUNX1; familial; leukemia; myelodysplastic syndrome.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Genetic Predisposition to Disease
  • Humans
  • Leukemia, Myeloid, Acute / diagnosis
  • Leukemia, Myeloid, Acute / genetics*
  • Leukemia, Myeloid, Acute / therapy*
  • Mutation
  • Myelodysplastic Syndromes / diagnosis
  • Myelodysplastic Syndromes / genetics*
  • Myelodysplastic Syndromes / therapy*
  • Translational Research, Biomedical*