New insights into the biology of acute myeloid leukemia with mutated NPM1.
Animals
Cell Nucleolus
/ metabolism
Cell Transformation, Neoplastic
/ genetics
Cytoplasm
/ metabolism
Frameshift Mutation
Gene Expression Regulation, Leukemic
Genes, Homeobox
Genomic Instability
Humans
Leukemia, Experimental
/ genetics
Leukemia, Myeloid, Acute
/ genetics
Mice
Mice, Transgenic
Molecular Targeted Therapy
Mutation, Missense
Neoplasm Proteins
/ antagonists & inhibitors
Nuclear Proteins
/ antagonists & inhibitors
Nucleophosmin
Protein Domains
Protein Isoforms
/ chemistry
Protein Transport
Structure-Activity Relationship
AML
Acute myeloid leukemia
B23
HOX
NPM1
XPO1
Journal
International journal of hematology
ISSN: 1865-3774
Titre abrégé: Int J Hematol
Pays: Japan
ID NLM: 9111627
Informations de publication
Date de publication:
Aug 2019
Aug 2019
Historique:
received:
11
12
2018
accepted:
25
12
2018
pubmed:
12
1
2019
medline:
10
1
2020
entrez:
12
1
2019
Statut:
ppublish
Résumé
Acute myeloid leukemia (AML), the most common acute leukemia in adults, increases exponentially with age. While a number of recent advances have improved treatment, high cure rates have not yet been achieved. Nucleophosmin (NPM1) is found mutated in nearly one-third of newly diagnosed cases and leads to NPM1 protein that is mislocalized to the cytoplasm instead of the nucleolus. If the mechanistic basis through which this mislocalization leads to malignancy could be revealed, this AML subtype may be targetable with new drugs. Here, we review the structure and functions of the normal and mutant forms of nucleophosmin. We discuss several recent studies that have shed light on the pathophysiology of NPM1 mutations. We discuss the importance of HOX gene misregulation in NPM1-mutated leukemias, as well as evidence for the reliance of mutated NPM1 on its continued nuclear export. Together, these aspects, as well as new tools to manipulate and study NPM1, open the door to new therapeutic strategies that may ultimately improve treatment of this common subtype of AML.
Identifiants
pubmed: 30632059
doi: 10.1007/s12185-018-02578-7
pii: 10.1007/s12185-018-02578-7
doi:
Substances chimiques
NPM1 protein, human
0
Neoplasm Proteins
0
Npm1 protein, mouse
0
Nuclear Proteins
0
Protein Isoforms
0
Nucleophosmin
117896-08-9
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
150-160Subventions
Organisme : NCI NIH HHS
ID : R01 CA183252
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK092883
Pays : United States
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