Cytoplasmic nucleophosmin in acute myelogenous leukemia with a normal karyotype.
Cytoplasmic nucleophosmin in acute myelogenous leukemia with a normal karyotype.
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DOI：
10.1056/nejmoa041974
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发表时间：
2005-01-20
影响因子：
158.5
通讯作者：
Martelli, MF
中科院分区：
文献类型：
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作者：
Falini, B;Mecucci, C;Martelli, MF
背景：核磷蛋白（NPM）是一种具有显著核仁定位的核质穿梭蛋白，调节ARF-p53肿瘤抑制通路。涉及NPM基因的易位导致NPM蛋白质的胞质错位。方法：我们用免疫组化方法研究了591例原发性急性髓细胞性白血病（AML）患者骨髓活检标本中NPM的亚细胞定位。然后，我们与细胞质NPM的存在与临床和生物学特征的diseases.RESULTS：细胞质NPM检测到208（35.2%）的591例标本原发性AML患者，但没有在135继发性AML标本或980造血或造血外肿瘤以外的AML。它与广泛的疾病形态学亚型、正常核型和诱导化疗的反应性相关，但与复发性遗传异常无关。有一个高频率的FLT 3内部串联重复和缺乏的CD 34和CD 133的AML标本与正常核型和细胞质脱位的NPM，但不是在那些蛋白质被限制在细胞核。AML标本与细胞质NPM携带突变的NPM基因，预测改变蛋白质在其C-末端，这种突变基因引起的NPM在转染cells.CONCLUSIONS：细胞质NPM是一个大的亚组AML患者的一个特征，他们有一个正常的核型，NPM基因突变，并对诱导化疗的反应。
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.