|
|
Blood, 1 February 2007, Vol. 109, No. 3, pp. 874-885.
Prepublished online as a Blood First Edition Paper on October 2, 2006; DOI 10.1182/blood-2006-07-012252.
 Previous Article | Table of Contents | Next Article 
REVIEWS IN TRANSLATIONAL HEMATOLOGY
Acute myeloid leukemia carrying cytoplasmic/mutated nucleophosmin (NPMc+ AML): biologic and clinical features
Brunangelo Falini1,
Ildo Nicoletti2,
Massimo F. Martelli1, and
Cristina Mecucci1
1 Institutes of Hematology and
2 Internal Medicine, University of Perugia, Perugia, Italy
The nucleophosmin (NPM1) gene encodes for a multifunctional nucleocytoplasmic shuttling protein that is localized mainly in the nucleolus. NPM1 mutations occur in 50% to 60% of adult acute myeloid leukemia with normal karyotype (AML-NK) and generate NPM mutants that localize aberrantly in the leukemic-cell cytoplasm, hence the term NPM-cytoplasmic positive (NPMc+ AML). Cytoplasmic NPM accumulation is caused by the concerted action of 2 alterations at mutant C-terminus, that is, 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 females, wide morphologic spectrum, multilineage involvement, high frequency of FLT3-ITD, CD34 negativity, and a distinct gene-expression profile. Analysis of mutated NPM has important clinical and pathologic 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 favorable 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 antileukemic drugs.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
I. H. I. M. Hollink, M. M. van den Heuvel-Eibrink, M. Zimmermann, B. V. Balgobind, S. T. C. J. M. Arentsen-Peters, M. Alders, A. Willasch, G. J. L. Kaspers, J. Trka, A. Baruchel, et al.
Clinical relevance of Wilms tumor 1 gene mutations in childhood acute myeloid leukemia
Blood,
June 4, 2009;
113(23):
5951 - 5960.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
U. Bacher, A. Kohlmann, and T. Haferlach
Perspectives of gene expression profiling for diagnosis and therapy in haematological malignancies
Brief Funct Genomic Proteomic,
May 27, 2009;
(2009)
elp011v1.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Schneider, E. Hoster, M. Unterhalt, S. Schneider, A. Dufour, T. Benthaus, G. Mellert, E. Zellmeier, S. K. Bohlander, M. Feuring-Buske, et al.
NPM1 but not FLT3-ITD mutations predict early blast cell clearance and CR rate in patients with normal karyotype AML (NK-AML) or high-risk myelodysplastic syndrome (MDS)
Blood,
May 21, 2009;
113(21):
5250 - 5253.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Meloni, M. Mancini, V. Gianfelici, M. P. Martelli, R. Foa, and B. Falini
Late relapse of acute myeloid leukemia with mutated NPM1 after eight years: evidence of NPM1 mutation stability
Haematologica,
February 1, 2009;
94(2):
298 - 300.
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Facchetti, S. A. Pileri, C. Agostinelli, M. P. Martelli, M. Paulli, A. Venditti, M. F Martelli, and B. Falini
Cytoplasmic nucleophosmin is not detected in blastic plasmacytoid dendritic cell neoplasm
Haematologica,
February 1, 2009;
94(2):
285 - 288.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Akagi, S. Ogawa, M. Dugas, N. Kawamata, G. Yamamoto, Y. Nannya, M. Sanada, C. W. Miller, A. Yung, S. Schnittger, et al.
Frequent genomic abnormalities in acute myeloid leukemia/myelodysplastic syndrome with normal karyotype
Haematologica,
February 1, 2009;
94(2):
213 - 223.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. P. Martelli, V. Pettirossi, E. Bonifacio, F. Mezzasoma, N. Manes, D. Cecchini, M. Capanni, I. Gionfriddo, A. Liso, R. Pacini, et al.
Evidence for CD34+ Hematopoietic Progenitor Cell Involvement in Acute Myeloid Leukemia with NPM1 Gene Mutation: Implications for the Cell of Origin
Blood (ASH Annual Meeting Abstracts),
November 16, 2008;
112(11):
307 - 307.
[Abstract]
[Full Text]
|
|
|
|
|
|
|
T. S. Laughlin, M. W. Becker, J. L. Liesveld, D. A. Mulford, C. N. Abboud, P. Brown, and P. G. Rothberg
Rapid Method for Detection of Mutations in the Nucleophosmin Gene in Acute Myeloid Leukemia
J. Mol. Diagn.,
July 1, 2008;
10(4):
338 - 345.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Lo-Coco, A. Cuneo, F. Pane, D. Cilloni, D. Diverio, M. Mancini, N. Testoni, A. Bardi, B. Izzo, N. Bolli, et al.
Prognostic impact of genetic characterization in the GIMEMA LAM99P multicenter study for newly diagnosed acute myeloid leukemia
Haematologica,
July 1, 2008;
93(7):
1017 - 1024.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Jongen-Lavrencic, S. M. Sun, M. K. Dijkstra, P. J. M. Valk, and B. Lowenberg
MicroRNA expression profiling in relation to the genetic heterogeneity of acute myeloid leukemia
Blood,
May 15, 2008;
111(10):
5078 - 5085.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Ottone, E. Ammatuna, S. Lavorgna, N. I. Noguera, F. Buccisano, A. Venditti, L. Gianni, M. Postorino, G. Federici, S. Amadori, et al.
An Allele-Specific RT-PCR Assay to Detect Type A Mutation of the Nucleophosmin-1 Gene in Acute Myeloid Leukemia
J. Mol. Diagn.,
May 1, 2008;
10(3):
212 - 216.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Wertheim and A. Bagg
Nucleophosmin (NPM1) Mutations in Acute Myeloid Leukemia: An Ongoing (Cytoplasmic) Tale of Dueling Mutations and Duality of Molecular Genetic Testing Methodologies
J. Mol. Diagn.,
May 1, 2008;
10(3):
198 - 202.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Szankasi, M. Jama, and D. W. Bahler
A New DNA-Based Test for Detection of Nucleophosmin Exon 12 Mutations by Capillary Electrophoresis
J. Mol. Diagn.,
May 1, 2008;
10(3):
236 - 241.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Falini, M. P. Martelli, C. Mecucci, A. Liso, N. Bolli, B. Bigerna, A. Pucciarini, S. Pileri, G. Meloni, M. F. Martelli, et al.
Cytoplasmic mutated nucleophosmin is stable in primary leukemic cells and in a xenotransplant model of NPMc+ acute myeloid leukemia in SCID mice
Haematologica,
May 1, 2008;
93(5):
775 - 779.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Garzon, M. Garofalo, M. P. Martelli, R. Briesewitz, L. Wang, C. Fernandez-Cymering, S. Volinia, C.-G. Liu, S. Schnittger, T. Haferlach, et al.
Distinctive microRNA signature of acute myeloid leukemia bearing cytoplasmic mutated nucleophosmin
PNAS,
March 11, 2008;
105(10):
3945 - 3950.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Falini, C. Mecucci, G. Saglio, F. L. Coco, D. Diverio, P. Brown, F. Pane, M. Mancini, M. P. Martelli, S. Pileri, et al.
NPM1 mutations and cytoplasmic nucleophosmin are mutually exclusive of recurrent genetic abnormalities: a comparative analysis of 2562 patients with acute myeloid leukemia
Haematologica,
March 1, 2008;
93(3):
439 - 442.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. E. Gale, C. Green, C. Allen, A. J. Mead, A. K. Burnett, R. K. Hills, D. C. Linch, and on behalf of the Medical Research Council Adult Le
The impact of FLT3 internal tandem duplication mutant level, number, size, and interaction with NPM1 mutations in a large cohort of young adult patients with acute myeloid leukemia
Blood,
March 1, 2008;
111(5):
2776 - 2784.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. P. Kroschinsky, U. Schakel, R. Fischer, B. Mohr, U. Oelschlaegel, R. Repp, M. Schaich, S. Soucek, G. Baretton, G. Ehninger, et al.
Cup-like acute myeloid leukemia: new disease or artificial phenomenon?
Haematologica,
February 1, 2008;
93(2):
283 - 286.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. P. S. Rawat, S. Thoene, V. M. Naidu, N. Arseni, B. Heilmeier, K. Metzeler, K. Petropoulos, A. Deshpande, L. Quintanilla-Martinez, S. K. Bohlander, et al.
Overexpression of CDX2 perturbs HOX gene expression in murine progenitors depending on its N-terminal domain and is closely correlated with deregulated HOX gene expression in human acute myeloid leukemia
Blood,
January 1, 2008;
111(1):
309 - 319.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Zhang, J.-M. Navenot, N. M. Frilot, N. Fujii, and S. C. Peiper
Association of Nucleophosmin Negatively Regulates CXCR4-Mediated G Protein Activation and Chemotaxis
Mol. Pharmacol.,
November 1, 2007;
72(5):
1310 - 1321.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
N. Bolli, I. Nicoletti, M. F. De Marco, B. Bigerna, A. Pucciarini, R. Mannucci, M. P. Martelli, A. Liso, C. Mecucci, F. Fabbiano, et al.
Born to Be Exported: COOH-Terminal Nuclear Export Signals of Different Strength Ensure Cytoplasmic Accumulation of Nucleophosmin Leukemic Mutants
Cancer Res.,
July 1, 2007;
67(13):
6230 - 6237.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Falini, I. Nicoletti, N. Bolli, M. P. Martelli, A. Liso, P. Gorello, F. Mandelli, C. Mecucci, and M. F. Martelli
Translocations and mutations involving the nucleophosmin (NPM1) gene in lymphomas and leukemias
Haematologica,
April 1, 2007;
92(4):
519 - 532.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Dohner
Implication of the Molecular Characterization of Acute Myeloid Leukemia
Hematology,
January 1, 2007;
2007(1):
412 - 419.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
