Acute myeloid leukemia with mutated NPM1: diagnosis, prognosis and therapeutic perspectives

被引:69
作者
Falini, Brunangelo [1 ]
Sportoletti, Paolo [1 ]
Martelli, Maria Paola [1 ]
机构
[1] Univ Perugia, Inst Hematol, I-06122 Perugia, Italy
关键词
acute myeloid leukemia; antibodies; normal karyotype; Npm1; mutations; nucleophosmin; MINIMAL RESIDUAL DISEASE; ACUTE MYELOGENOUS LEUKEMIA; NUCLEOPHOSMIN GENE-MUTATIONS; NUCLEAR EXPORT SIGNAL; CYTOPLASMIC NUCLEOPHOSMIN; MYELODYSPLASTIC SYNDROME; QUANTITATIVE ASSESSMENT; CLINICAL-SIGNIFICANCE; TANDEM DUPLICATION; EXPRESSION PROFILE;
D O I
10.1097/CCO.0b013e3283313dfa
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose of review Nucleophosmin (NPM1) gene mutations, which cause aberrant cytoplasmic expression of nucleophosmin (NPMc+), are the most frequent genetic alteration in acute myeloid leukemia (AML), being found in about 30% cases. The present review summarizes recent advances in the biology, diagnosis, prognosis and therapy of NPM1-mutated AML. Recent findings Diagnostic criteria of NPM1-mutated AML are discussed in the light of its recent inclusion in the 2008 WHO classification of myeloid neoplasms. We also outline the most recent findings on prognosis and monitoring of minimal residual disease in NPM1-mutated AML and their implications for therapeutic decisions. Moreover, new insights are presented into the molecular mechanisms underlying perturbed nucleophosmin traffic in NPM1-mutated AML, which provides the rationale for the development of targeted therapies, Summary AML with mutated NPM1 is a leukemia entity with distinct molecular, pathological, and prognostic features.
引用
收藏
页码:573 / 581
页数:9
相关论文
共 85 条
[21]   Structural basis for leucine-rich nuclear export signal recognition by CRM1 [J].
Dong, Xiuhua ;
Biswas, Anindita ;
Sueel, Katherine E. ;
Jackson, Laurie K. ;
Martinez, Rita ;
Gu, Hongmei ;
Chook, Yuh Min .
NATURE, 2009, 458 (7242) :1136-U71
[22]   A novel quantitative assessment of minimal residual disease in patients with acute myeloid leukemia carrying NPM1 (nucleophosmin) exon 12 mutations [J].
Dvorakova, D. ;
Lengerova, M. ;
Pospisilova, J. ;
Palasek, I. ;
Mayer, J. .
LEUKEMIA, 2009, 23 (04) :793-796
[23]   Cytoplasmic nucleophosmin is not detected in blastic plasmacytoid dendritic cell neoplasm [J].
Facchetti, Fabio ;
Pileri, Stefano A. ;
Agostinelli, Claudio ;
Martelli, Maria Paola ;
Paulli, Marco ;
Venditti, Adriano ;
Martelli, Massimo F. ;
Falini, Brunangelo .
HAEMATOLOGICA-THE HEMATOLOGY JOURNAL, 2009, 94 (02) :285-288
[24]   Cytoplasmic nucleophosmin in acute myelogenous leukemia with a normal karyotype. [J].
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 ;
Martelli, MF .
NEW ENGLAND JOURNAL OF MEDICINE, 2005, 352 (03) :254-266
[25]   Therapy-related acute myeloid leukaemia with mutated NPM1:: treatment induced or de novo in origin? [J].
Falini, B. .
LEUKEMIA, 2008, 22 (05) :891-892
[26]   Cytoplasmic mutated nucleophosmin (NPM) defines the molecular status of a significant fraction of myeloid sarcomas [J].
Falini, B. ;
Lenze, D. ;
Hasserjian, R. ;
Coupland, S. ;
Jaehne, D. ;
Soupir, C. ;
Liso, A. ;
Martelli, M. P. ;
Bolli, N. ;
Bacci, F. ;
Pettirossi, V. ;
Santucci, A. ;
Martelli, M. F. ;
Pileri, S. ;
Stein, H. .
LEUKEMIA, 2007, 21 (07) :1566-1570
[27]  
FALINI B, 2009, LEUKEMIA
[28]   Cytoplasmic mutated nucleophosmin is stable in primary leukemic cells and in a xenotransplant model of NPMc+ acute myeloid leukemia in SCID mice [J].
Falini, Brunangelo ;
Martelli, Maria Paola ;
Mecucci, Cristina ;
Liso, Arcangelo ;
Bolli, Niccolo ;
Bigerna, Barbara ;
Pucciarini, Alessandra ;
Pileri, Stefano ;
Meloni, Giovanna ;
Martelli, Massimo F. ;
Haferlach, Torsten ;
Schnittger, Susanne .
HAEMATOLOGICA, 2008, 93 (05) :775-779
[29]   NPM1 mutations and cytoplasmic nucleophosmin are mutually exclusive of recurrent genetic abnormalities: a comparative analysis of 2562 patients with acute myeloid leukemia [J].
Falini, Brunangelo ;
Mecucci, Cristina ;
Saglio, Giuseppe ;
Lo Coco, Francesco ;
Diverio, Daniela ;
Brown, Patrick ;
Pane, Fabrizio ;
Mancini, Marco ;
Martelli, Maria Paola ;
Pileri, Stefano ;
Haferlach, Torsten ;
Haferlach, Claudia ;
Schnittger, Susanne .
HAEMATOLOGICA, 2008, 93 (03) :439-442
[30]   Any role for the nucleophosmin (NPM1) gene in myelodysplastic syndromes and acute myeloid leukemia with chromosome 5 abnormalities? [J].
Falini, Brunangelo .
LEUKEMIA & LYMPHOMA, 2007, 48 (11) :2093-2095