Table 2

Distinctive features of AML with mutated NPM1 (NPMc+ AML)

Genetic features
    NPM1 mutation* is specific for AML, mostly “de novo”
    Usually all leukemic cells carry the NPM1 mutation
    Mutually exclusive with other “AML with recurrent genetic abnormalities”
    NPM1 mutation is stable (consistently retained at relapse)
    NPM1 mutation usually precedes other associated mutations (eg, FLT3-ITD)
    Unique GEP signature (↓ CD34 gene; ↑ HOX genes)
    Distinct microRNA profile
Clinical, pathologic, immunophenotypic, and cytogenetic features
    Common in adult AML (∼ 30% of cases), less frequent in children (6.5%-8.4%)
    Higher incidence in female
    Close association with normal karyotype (∼ 85% of cases)
    ∼ 15% of cases carry chromosome aberrations, especially +8, del9(q), +4
    Wide morphologic spectrum (more often M4 and M5)
    Frequent multilineage involvement
    Negativity for CD34 (90%-95% of cases)§
    Good response to induction therapy
    Relatively good prognosis (in the absence of FLT3-ITD)
  • GEP indicates gene expression profiling.

  • * Or its immunohistologic surrogate (cytoplasmic NPM, NPMc+).

  • Lower incidence in Chinese children.

  • In most, but not all, studies.

  • § Less than 10% CD34+ cells.