Nucleophosmin: a versatile molecule associated with hematological malignancies.
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.
Naoe
Tomoki
T
Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan. tnaoe@med.nagoya-u.ac.jp
Suzuki
Tatsuya
T
Kiyoi
Hitoshi
H
Urano
Takeshi
T
D000818:Animals; D016368:Frameshift Mutation; D006238:Haploidy; D019337:Hematologic Neoplasms / Q000235:genetics*; D006801:Humans; D017728:Lymphoma, Large-Cell, Anaplastic / Q000235:genetics; D009363:Neoplasm Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D000090243:Nucleophosmin; D015514:Oncogene Proteins, Fusion / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D011487:Protein Conformation; D011505:Protein-Tyrosine Kinases / Q000032:analysis / Q000235:genetics / Q000378:metabolism
C120276:NPM-RARalpha protein, human; C000716967:NPM1 protein, human; D009363:Neoplasm Proteins; C000715570:Npm1 protein, mouse; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; D000090243:Nucleophosmin; C107023:p80(NPM-ALK) protein; D011505:Protein-Tyrosine Kinases