Cytoplasmic Nucleophosmin in Acute Myelogenous Leukemia with a Normal Karyotype
Open accessAbstract
BACKGROUND: Nucleophosmin (NPM), a nucleocytoplasmic shuttling protein with prominent nucleolar localization, regulates the ARF-p53 tumor-suppressor pathway. Translocations involving the NPM gene cause cytoplasmic dislocation of the NPM protein. METHODS: We used immunohistochemical methods to study the subcellular localization of NPM in bone marrow-biopsy specimens from 591 patients with primary acute myelogenous leukemia (AML). We then correlated the presence of cytoplasmic NPM with clinical and biologic features of the disease. RESULTS: Cytoplasmic NPM was detected in 208 (35.2 percent) of the 591 specimens from patients with primary AML but not in 135 secondary AML specimens or in 980 hematopoietic or extrahematopoietic neoplasms other than AML. It was associated with a wide spectrum of morphologic subtypes of the disease, a normal karyotype, and responsiveness to induction chemotherapy, but not with recurrent genetic abnormalities. There was a high frequency of FLT3 internal tandem duplications and absence of CD34 and CD133 in AML specimens with a normal karyotype and cytoplasmic dislocation of NPM, but not in those in which the protein was restricted to the nucleus. AML specimens with cytoplasmic NPM carried mutations of the NPM gene that were predicted to alter the protein at its C-terminal; this mutant gene caused cytoplasmic localization of NPM in transfected cells. CONCLUSIONS: Cytoplasmic NPM is a characteristic feature of a large subgroup of patients with AML who have a normal karyotype, NPM gene mutations, and responsiveness to induction chemotherapy.
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NPM1 is one of the most commonly mutated genes in AML, occurring in approximately 50% of adult and 20% of childhood AML with normal karyotypes.
“Nucleophosmin (NPM1) is one of the most commonly mutated genes in AML, occurring in approximately 50% of adult and 20% of childhood AML with normal karyotypes [193, 194].”
From Proteolysis targeting chimeras (PROTACs) are emerging therapeutics for hematologic malignancies (2020) · cites this paper as [193]
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- Authors
- Falini, B., Mecucci, C., Tiacci, E., Alcalay, M., Rosati, R., Pasqualucci, L., La Starza, R., Diverio, D., Colombo, E., Santucci, A., Bigerna, B., Pacini, R., Pucciarini, A., Liso, A., Vignetti, M., Fazi, P., Meani, N., Pettirossi, V., Saglio, G., Mandelli, F., Lo-Coco, F., Pelicci, P.-G., & Martelli, M. F.
- Affiliations
- University of Perugia (IT)
- European Institute of Oncology (IT)
- Sapienza University of Rome (IT)
- University of Foggia (IT)
- Ospedale San Luigi Gonzaga (IT)
- ORCID
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2005-01-20
- Volume
- 352
- Issue
- 3
- Pages
- 254-266
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2170515966
- Cited by
- 1,892
- References
- 43
- Citations by year
- 2026: 56 · 2025: 64 · 2024: 72 · 2023: 86 · 2022: 89 · 2021: 101 · 2020: 82 · 2019: 87 · 2018: 65 · 2017: 77 · 2016: 84 · 2015: 94 · 2014: 105 · 2013: 107 · 2012: 99
- FWCI
- 57.77
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Cineca Institutional Research Information System (Tor Vergata University) (submittedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- INFM-OAR (INFN Catania) (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
- Health Sciences › Medicine › Hematology › Chronic Myeloid Leukemia Treatments
- Keywords
- nucleophosmin, acute myeloid leukemia, normal karyotype, FLT3-ITD, induction chemotherapy response, ARF-p53 pathway, CD34, CD133, subcellular protein localization
- MeSH terms
- Nucleophosmin, Adolescent, Adult, Antibodies, Monoclonal, Antineoplastic Agents, Base Sequence, Bone Marrow, Cell Nucleolus, Cytoplasm, DNA Mutational Analysis, Humans, Karyotyping, Middle Aged, Mutation, Nuclear Proteins, Remission Induction, Transfection, Translocation, Genetic, Leukemia, Myeloid, Acute
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