Open AccessNucleophosmin: A versatile molecule associated with hematological malignancies
Author(s) -
Naoe Tomoki,
Suzuki Tatsuya,
Kiyoi Hitoshi,
Urano Takeshi
Publication year - 2006
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2006.00270.x
Subject(s) - nucleophosmin , npm1 , biology , cancer research , carcinogenesis , anaplastic large cell lymphoma , gene mutation , leukemia , gene duplication , mutation , myeloid leukemia , gene , lymphoma , genetics , karyotype , immunology , chromosome
Nucleophosmin (NPM) is a nucleolar phosphoprotein that plays multiple roles in ribosome assembly and transport, cytoplasmic–nuclear trafficking, centrosome duplication and regulation of p53. In hematological malignancies, the NPM1 gene is frequently involved in chromosomal translocation, mutation and deletion. The NPM1 gene on 5q35 is translocated with the anaplastic lymphoma kinase ( ALK ) gene in anaplastic large cell lymphoma with t(2;5). The MLF1 and RARA genes are fused with NPM1 in myelodysplastic syndrome and acute myeloid leukemia (AML) with t(3;5) and acute promyelocytic leukemia with t(5;17), respectively. In each fused protein, the N‐terminal NPM portion is associated with oligomerization of a partner protein leading to altered signal transduction or transcription. Recently, mutations of exon 12 have been found in a significant proportion of de novo AML, especially in those with a normal karyotype. Mutant NPM is localized aberrantly in the cytoplasm, but the molecular mechanisms for leukemia remain to be studied. Studies of knock‐out mice have revealed new aspects regarding NPM1 as a tumor‐suppressor gene. This review focuses on the clinical significance of the NPM1 gene in hematological malignancies and newly discovered roles of NPM associated with oncogenesis. ( Cancer Sci 2006; 97: 963–969)