Acute myeloid leukemia with mutated nucleophosmin (NPM1): is it a distinct entity?

Blood. 2011 Jan 27;117(4):1109-20. doi: 10.1182/blood-2010-08-299990. Epub 2010 Oct 28.

Abstract

After the discovery of NPM1-mutated acute myeloid leukemia (AML) in 2005 and its subsequent inclusion as a provisional entity in the 2008 World Health Organization classification of myeloid neoplasms, several controversial issues remained to be clarified. It was unclear whether the NPM1 mutation was a primary genetic lesion and whether additional chromosomal aberrations and multilineage dysplasia had any impact on the biologic and prognostic features of NPM1-mutated AML. Moreover, it was uncertain how to classify AML patients who were double-mutated for NPM1 and CEBPA. Recent studies have shown that: (1) the NPM1 mutant perturbs hemopoiesis in experimental models; (2) leukemic stem cells from NPM1-mutated AML patients carry the mutation; and (3) the NPM1 mutation is usually mutually exclusive of biallelic CEPBA mutations. Moreover, the biologic and clinical features of NPM1-mutated AML do not seem to be significantly influenced by concomitant chromosomal aberrations or multilineage dysplasia. Altogether, these pieces of evidence point to NPM1-mutated AML as a founder genetic event that defines a distinct leukemia entity accounting for approximately one-third of all AML.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Founder Effect
  • Humans
  • Leukemia, Myeloid, Acute / classification*
  • Leukemia, Myeloid, Acute / diagnosis
  • Leukemia, Myeloid, Acute / genetics*
  • Models, Biological
  • Mutant Proteins / genetics
  • Mutant Proteins / metabolism
  • Mutant Proteins / physiology
  • Mutation* / physiology
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • Nucleophosmin
  • Prognosis

Substances

  • Mutant Proteins
  • NPM1 protein, human
  • Nuclear Proteins
  • Nucleophosmin