ALK-positive diffuse large B-cell lymphoma is associated with Clathrin-ALK rearrangements:: report of 6 cases
ALK-positive diffuse large B-cell lymphoma is associated with Clathrin-ALK rearrangements:: report of 6 cases
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DOI：
10.1182/blood-2003-03-0786
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发表时间：
2003-10-01
期刊：
影响因子：
20.3
通讯作者：
Delsol, G
中科院分区：
文献类型：
--
作者：
Gascoyne, RD;Lamant, L;Delsol, G
淋巴细胞ALK蛋白的表达和变异型间变性淋巴瘤激酶(ALK)易位的描述通常仅限于T细胞和零间变性大细胞淋巴瘤(ALCL)。所有这些病例都是由染色体2p23上的ALK基因和5q35或其他变异易位伙伴上的NPM造成的一种新的融合。弥漫性大B细胞淋巴瘤(DLBCL)的一种罕见变种，最初于1997年被描述，被认为过度表达全长ALK，而不是ALCL特有的嵌合蛋白。然而，全长的ALK蛋白缺乏酪氨酸激酶活性，因此肿瘤发生的机制仍然难以捉摸。我们描述了6例ALK(+)DLBCL，其特征是一个简单或复杂的t(2；17)(p23；q23)，涉及位于染色体17q23带的clathrin基因(Cltc)和位于染色体带2p23的alk基因。所有病例均进行了荧光原位杂交(FISH)，其中1例辅以标准细胞遗传学分析、多色核型分析(M-FISH)和逆转录聚合酶链式反应。这些结果清楚地表明，大多数ALK(+)DLBCL具有相同的ALK表达失控机制。此外，这些结果表明在这些肿瘤中存在Cltc-ALK融合，并将与这种遗传异常相关的疾病扩展到包括经典T细胞或ALCL缺失、ALK(+)DLBCL和炎症性肌纤维母细胞瘤。(C)2003年，由美国血液病学会提供。
Expression of ALK protein by lymphoid cells and the description of variant anaplastic lymphoma kinase (ALK) translocations have typically been restricted to cases of T-cell and null anaplastic large-cell lymphoma (ALCL). All such cases result from a novel fusion created by the ALK gene on chromosome 2p23 and NPM on 5q35 or other variant translocation partners. A rare variant of diffuse large B-cell lymphoma (DLBCL), originally described in 1997, was thought to overexpress full-length ALK in contrast to a chimeric protein characteristic of ALCL. However, full-length ALK protein lacks tyrosine kinase activity and thus the mechanism of oncogenesis has remained elusive. We describe 6 cases of ALK(+) DLBCL characterized by a simple or complex t(2;17)(p23;q23) involving the clathrin gene (CLTC) at chromosome band 17q23 and the ALK gene at chromosome band 2p23. All cases were studied using fluorescence in situ hybridization (FISH), complemented in one case with standard cytogenetic analysis, multicolor karyotyping (M-FISH), and reverse transcriptase-polymerase chain reaction. These results clearly demonstrate that most cases of ALK(+) DLBCL share the same mechanism of deregulated ALK expression. Moreover, these results demonstrate the presence of CLTC-ALK fusions in these tumors and extend the list of diseases associated with this genetic abnormality to include classical T-cell or null ALCL, ALK(+) DLBCL, and inflammatory myofibroblastic tumors. (C) 2003 by The American Society of Hematology.