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

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.

journal_name

Blood

journal_title

Blood

authors

Falini B,Martelli MP,Bolli N,Sportoletti P,Liso A,Tiacci E,Haferlach T

doi

10.1182/blood-2010-08-299990

subject

Has Abstract

pub_date

2011-01-27 00:00:00

pages

1109-20

issue

4

eissn

0006-4971

issn

1528-0020

pii

blood-2010-08-299990

journal_volume

117

pub_type

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