Multilineage dysplasia has no impact on biologic, clinicopathologic, and prognostic features of AML with mutated nucleophosmin (NPM1)

被引：90

作者：

Falini, Brunangelo ^{[1
]}

Macijewski, Katja ^{[2
]}

Weiss, Tamara ^{[2
]}

Bacher, Ulrike ^{[3
]}

Schnittger, Susanne ^{[2
]}

Kern, Wolfgang ^{[2
]}

Kohlmann, Alexander ^{[2
]}

Klein, Hans-Ulrich ^{[4
]}

Vignetti, Marco ^{[5
]}

Piciocchi, Alfonso ^{[5
]}

Fazi, Paola ^{[5
]}

Martelli, Maria Paola ^{[1
]}

Vitale, Antonella ^{[5
]}

Pileri, Stefano ^{[6
]}

Miesner, Miriam ^{[2
]}

Santucci, Antonella ^{[1
]}

Haferlach, Claudia ^{[2
]}

Mandelli, Franco ^{[5
]}

Haferlach, Torsten ^{[2
]}

机构：

[1] Univ Perugia, Inst Hematol, I-06100 Perugia, Italy

[2] Munich Leukemia Lab GmbH, Munich, Germany

[3] Univ Canc Ctr Hamburg, Dept Stem Cell Transplantat, Hamburg, Germany

[4] Univ Munster, Dept Med Informat & Bioinformat, Munster, Germany

[5] GIMEMA Fdn, GIMEMA Data Ctr, Rome, Italy

[6] Univ Bologna, Inst Pathol, Hematopathol Sect, Policlin S Orsola, Bologna, Italy

来源：

BLOOD | 2010年 / 115卷 / 18期

关键词：

ACUTE MYELOID-LEUKEMIA; ACUTE MYELOGENOUS LEUKEMIA; GENE-EXPRESSION PROFILE; CYTOPLASMIC NUCLEOPHOSMIN; ADULT PATIENTS; NPMC(+) AML; MUTATIONS; MUTANT; CLASSIFICATION; RELEVANCE;

D O I：

10.1182/blood-2009-08-240457

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

NPM1-mutated acute myeloid leukemia (AML) is a provisional entity in the 2008 World Health Organization (WHO) classification of myeloid neoplasms. The significance of multilineage dysplasia (MLD) in NPM1-mutated AML is unclear. Thus, in the 2008 WHO classification, NPM1-mutated AML with MLD is classified as AML with myelodysplasia (MD)-related changes (MRCs). We evaluated morphologically 318 NPM1-mutated AML patients and found MLD in 23.3%. Except for a male predominance and a lower fms-related tyrosine kinase 3-internal tandem duplication (FLT3-ITD) incidence in the MLD+ group, no differences were observed in age, sex, cytogenetics, and FLT3-tyrosine kinase domain between NPM1-mutated AML with and without MLD. NPM1-mutated AML with and without MLD showed overlapping immuno-phenotype (CD34 negativity) and gene expression profile (CD34 down-regulation, HOX genes up-regulation). Moreover, overall and event-free survival did not differ among NPM1-mutated AML patients independently of whether they were MLD+ or MLD-, the NPM1-mutated/FLT3-ITD negative genotype showing the better prognosis. Lack of MLD impact on survival was confirmed by multivariate analysis that highlighted FLT3-ITD as the only significant prognostic parameter in NPM1-mutated AML. Our findings indicate that NPM1 mutations rather than MLD dictate the distinctive features of NPM1-mutated AML. Thus, irrespective of MLD, NPM1-mutated AML represents one disease entity clearly distinct from AML with MRCs. (Blood. 2010; 115(18):3776-3786)

引用

页码：3776 / 3786

页数：11

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