Table 2.

WHO classification of myeloid neoplasms with germ line predisposition and guide for molecular genetic diagnostics

WHO classification
 Myeloid neoplasms with germ line predisposition without a preexisting disorder or organ dysfunction
  AML with germ line CEBPA mutation
  Myeloid neoplasms with germ line DDX41 mutation
 Myeloid neoplasms with germ line predisposition and preexisting platelet disorders
  Myeloid neoplasms with germ line RUNX1 mutation
  Myeloid neoplasms with germ line ANKRD26 mutation
  Myeloid neoplasms with germ line ETV6 mutation
 Myeloid neoplasms with germ line predisposition and other organ dysfunction
  Myeloid neoplasms with germ line GATA2 mutation
  Myeloid neoplasms associated with bone marrow failure syndromes
  Juvenile myelomonocytic leukemia associated with neurofibromatosis, Noonan syndrome, or Noonan syndrome-like disorders
  Myeloid neoplasms associated with Noonan syndrome
  Myeloid neoplasms associated with Down syndrome
Guide for molecular genetic diagnostics
 Myelodysplastic predisposition/acute leukemia predisposition syndromes
  CEBPA, DDX41, RUNX1, ANKRD26, ETV6, GATA2, SRP72, 14q32.2 genomic duplication (ATG2B/GSKIP)
 Cancer predisposition syndromes§
  Li Fraumeni syndrome (TP53)
  Germ line BRCA1/BRCA2 mutations
 Bone marrow failure syndromes
  Dyskeratosis congenita (TERC, TERT)
  Fanconi anemia
  • Classification portion of table is adopted from Arber et al.3

  • * Recognition of familial myeloid neoplasms requires that physicians take a thorough patient and family history to assess for typical signs and symptoms of known syndromes, including data on malignancies and previous bleeding episodes. See also Churpek and Godley27 for how to identify, test, and counsel individuals and families suspected of having an inherited myeloid malignancy syndrome.

  • Lymphoid neoplasms also reported.

  • Molecular genetic diagnostics are guided by a detailed patient and family history27; diagnostics should be performed in close collaboration with a genetic counselor; patients with a suspected heritable myeloid neoplasm, who test negative for known predisposition genes, should ideally be entered on a research study to facilitate new syndrome discovery.

  • § Mutations in genes associated with cancer predisposition genes such as TP53 and BRCA1/2 appear to be frequent in therapy-related myeloid neoplasms.256