ABSTRACT
Heterozygous mutation of the nucleophosmin gene [NPM1] has recently been described as one of the most frequent genetic lesions in acute myeloid leukemia [AML]. NPM1 gene mutations tend to occur more frequently in women, and also tend to be associated with a higher white blood cell count. There is no significant age difference. NPM1-mutated AML is preferentially associated with AML monocytic differentiation [in particular FAB M5b], lack of CD34, normal cytogenetics, FLT3 gene mutations, and a trend toward favorable clinical outcome, specially in patients without FLT3 gene mutation. NPM1 gene mutations cause a framshift in the C-terminus of exon 12, disrupting the NPM nucleolar-localization signal or generating leucin-rich nuclear export motif, resulting in abnormal cytoplasmic accumulation of NPM. Detection of NPM1 gene mutation may allow dissection of the heterogeneous group of AML with normal karyotype into prognostically different subgroups. Exploring the mechanisms may lead to a better understanding of how mutant NPM protein becomes leukemogenic, thereby providing insights for the development of new chemotherapeutic agents