Multilineage dysplasia has no impact on biologic, clinicopathologic, and prognostic features of AML with mutated nucleophosmin (NPM1)
Multilineage dysplasia has no impact on biologic, clinicopathologic, and prognostic features of AML with mutated nucleophosmin (NPM1)
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DOI：
10.1182/blood-2009-08-240457
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发表时间：
2010-05-06
期刊：
影响因子：
20.3
通讯作者：
Haferlach, Torsten
中科院分区：
文献类型：
--
作者：
Falini, Brunangelo;Macijewski, Katja;Haferlach, Torsten
NPM1 突变的急性髓系白血病 (AML) 是 2008 年世界卫生组织 (WHO) 髓系肿瘤分类中的一个临时实体。多系发育不良 (MLD) 在 NPM1 突变的 AML 中的意义尚不清楚。因此，在 2008 年 WHO 分类中，NPM1 突变伴 MLD 的 AML 被归类为伴骨髓增生异常 (MD) 相关变化 (MRC) 的 AML。我们对 318 名 NPM1 突变的 AML 患者进行了形态学评估，发现 23.3% 患有 MLD。除了MLD+组中男性占主导地位和fms相关酪氨酸激酶3-内部串联重复（FLT3-ITD）发生率较低外，伴和不伴MLD的NPM1突变AML之间在年龄、性别、细胞遗传学和FLT3-酪氨酸激酶结构域方面没有观察到差异。伴有和不伴有 MLD 的 NPM1 突变 AML 表现出重叠的免疫表型（CD34 阴性）和基因表达谱（CD34 下调，HOX 基因上调）。此外，NPM1 突变的 AML 患者的总体生存率和无事件生存率没有差异，无论他们是 MLD+ 还是 MLD-，NPM1 突变/FLT3-ITD 阴性基因型显示出更好的预后。多变量分析证实了 MLD 对生存没有影响，强调 FLT3-ITD 是 NPM1 突变 AML 中唯一重要的预后参数。我们的研究结果表明，NPM1 突变而非 MLD 决定了 NPM1 突变 AML 的独特特征。因此，无论MLD如何，NPM1突变的AML代表了一种与具有MRC的AML明显不同的疾病实体。 （血。2010；115（18）：3776-3786）
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)