Germ line predisposition to myeloid malignancies appearing in adulthood

Expert Rev Hematol. 2018 Aug;11(8):625-636. doi: 10.1080/17474086.2018.1494566. Epub 2018 Jul 23.


Germ line predisposition to myeloid neoplasms has been incorporated in the WHO 2016 classification of myeloid neoplasms and acute leukemia. The new category of disease is named hereditary myeloid disorder (HMD). Although most myeloid neoplasms are sporadic, germ line mutations and familial predisposition can contribute to development of chronic myeloid diseases and acute myeloid leukemia. This finding and upcoming frequent use of genome wide detection of molecular aberrations will lead to a higher detection rate of a genetic predisposition and influence treatment decisions. Hereditary predisposition is responsible for 5-10% of myeloid malignancies. Management of affected patients begins by the awareness of treating physicians of the problem and a precise work up of the patient and family members. Areas covered: This review focuses on current knowledge about germ line predisposition for myeloid neoplasms including diagnostic, prognostic, and therapeutic aspects in adult patients. Essential information for clinical routine is provided. Expert commentary: Compared to a patient without predisposition, adaptation of treatment strategy for patients with an HMD is often necessary, especially to avoid higher risk of relapse or higher toxicity during chemotherapy or transplantation. Mistakes in choice of a related donor can be omitted. Relatives at risk of developing a HMD need specific surveillance.

Keywords: Germ line mutation; WHO classification; acute myeloid leukemia; familial predisposition; inherited bone marrow failure; myelodysplastic syndromes; myeloproliferative neoplasm.

Publication types

  • Review

MeSH terms

  • Adult
  • Animals
  • Biomarkers, Tumor
  • Clinical Decision-Making
  • Genetic Association Studies
  • Genetic Predisposition to Disease*
  • Germ-Line Mutation*
  • Humans
  • Leukemia, Myeloid, Acute / diagnosis*
  • Leukemia, Myeloid, Acute / genetics*
  • Myelodysplastic Syndromes / diagnosis
  • Myelodysplastic Syndromes / genetics
  • Myeloproliferative Disorders / diagnosis*
  • Myeloproliferative Disorders / genetics*


  • Biomarkers, Tumor