Inghirami G, Macri L, Cesarman E, Chadburn A, Zhong J, Knowles D M
Division of Surgical Pathology, College of Physicians and Surgeons of Columbia University, New York, NY.
Blood. 1994 Jun 15;83(12):3581-90.
Anaplastic large-cell lymphoma (ALCL) represents a morphologically distinct type of non-Hodgkin's lymphoma (NHL) characterized phenotypically by the expression of the CD30 antigen, a new member of the nerve growth factor gene family. The lymphoid origin of ALCL has been documented using immunohistochemical and molecular genetic analyses. However, very little is known so far regarding the precise pathogenetic mechanisms involved in its development and progression. Therefore, we investigated bcl-2, p53, and retinoblastoma gene (Rb) expression immunohistochemically; the occurrence of bcl-2, c-myc, and Rb gene rearrangements using Southern blotting; and the presence of ras and p53 gene somatic mutations by single-strand conformation polymorphism assay in a panel of 18 well-characterized ALCLs. In addition, the presence of Epstein-Barr (EBV) and human T-cell lymphotropic virus type I (HTLV-I) genomes were investigated using polymerase chain reaction. We identified abnormal c-myc gene products in 6 of 18 cases (33%) of ALCL. On the other hand, the bcl-2 and Rb genes were not rearranged and K-, N-, and H-ras gene somatic mutations were not found. Significant levels of p53 protein expression were found in more than 60% of ALCLs, but only a single ALCL carried a p53 gene mutation (exon 5). Only 3 ALCL cases, all occurring in human immunodeficiency virus-infected patients, were positive for EBV genomes. On the other hand, contrary to previous findings, no HTLV-I products could be identified. Despite the fact that the c-myc proto-oncogene appears to be frequently altered in ALCL, no pathognomonic abnormality could be identified and therefore additional studies and new strategies should be designed to identify the pathogenetic mechanisms involved in the development of ALCL.
间变性大细胞淋巴瘤（ALCL）是一种形态学上独特的非霍奇金淋巴瘤（NHL），其表型特征为神经生长因子基因家族的新成员CD30抗原的表达。已通过免疫组织化学和分子遗传学分析证明了ALCL的淋巴样起源。然而，迄今为止，对于其发生和发展所涉及的精确发病机制知之甚少。因此，我们采用免疫组织化学方法研究了bcl-2、p53和视网膜母细胞瘤基因（Rb）的表达；采用Southern印迹法检测了bcl-2、c-myc和Rb基因重排的发生情况；采用单链构象多态性分析检测了18例特征明确的ALCL中ras和p53基因的体细胞突变情况。此外，还采用聚合酶链反应研究了爱泼斯坦-巴尔病毒（EBV）和I型人类T细胞嗜淋巴细胞病毒（HTLV-I）基因组的存在情况。我们在18例ALCL病例中的6例（33%）中鉴定出异常的c-myc基因产物。另一方面，bcl-2和Rb基因未发生重排，未发现K-、N-和H-ras基因的体细胞突变。在60%以上的ALCL中发现了高水平的p53蛋白表达，但只有1例ALCL携带p53基因突变（第5外显子）。仅3例ALCL病例（均发生在感染人类免疫缺陷病毒的患者中）的EBV基因组呈阳性。另一方面，与先前的发现相反，未鉴定出HTLV-I产物。尽管c-myc原癌基因在ALCL中似乎经常发生改变，但未发现特征性异常，因此应设计更多研究和新策略来确定ALCL发生发展所涉及的发病机制。
