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Blood.
2006 Oct 2; [Epub ahead of print]
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Acute myeloid leukemia carrying cytoplasmic/mutated
nucleophosmin (NPMc+ AML): biological and clinical
features.
Falini B, Nicoletti I, Martelli MF,
Mecucci C.
University of Perugia,
Italy.
The Nucleophosmin (NPM1) gene
encodes for a multifunctional nucleo-cytoplasmic
shuttling protein which is mainly localized in the
nucleolus. NPM1 mutations occur in 50-60% of adult
acute myeloid leukemia with normal karyotype (AML-NK)
and generate NPM mutants that localize aberrantly in
the leukemic cells cytoplasm; hence the term
NPM-cytoplasmic positive (NPMc+ AML). Cytoplasmic
NPM accumulation is caused by the concerted action
of two alterations at mutant C-terminus, i.e.
changes of tryptophan(s) 288 and 290 (or only 290)
and creation of an additional nuclear export signal
(NES) motif. NPMc+ AML shows increased frequency in
adults and female sex, wide morphologic spectrum,
multilineage involvement, high frequency of
FLT3-ITD, CD34-negativity, and distinct gene
expression profile. Analysis of mutated NPM has
important clinical and pathological applications.
Immunohistochemical detection of cytoplasmic NPM
predicts NPM1 mutations and helps rationalize
cytogenetic/molecular studies in AML. NPM1 mutations
in absence of FLT3-ITD identify a prognostically
favourable subgroup in the heterogeneous AML-NK
category. Due to their frequency and stability, NPM1
mutations may become a new tool for monitoring
minimal residual disease in AML-NK. Future studies
should focus on clarifying how NPM mutants promote
leukemia, integrating NPMc+ AML in the upcoming
World Health Organization leukemia classification,
and eventually developing specific anti-leukemic
drugs.
PMID: 17008539 [PubMed - as supplied
by publisher]