Kadin M E, Morris S W
Department of Pathology, Beth Israel Hospital and Harvard Medical School, Boston, MA 02115, USA.
Leuk Lymphoma. 1998 Apr;29(3-4):249-56. doi: 10.3109/10428199809068562.
A recurrent, reciprocal balanced translocation, t(2;5) (p23;q35), has been recognized in CD30+ anaplastic large-cell lymphomas (ALCL), a newly recognized subtype comprising approximately 5% of all non-Hodgkin's lymphoma (NHL). This translocation creates a novel fusion protein, NPM-ALK, which has transforming properties in vitro and can cause large-cell lymphoma in vivo when transfected into murine bone marrow. Multiple techniques including reverse transcriptase-polymerase chain reaction (RT-PCR) amplification of NPM-ALK fusion transcripts, genomic DNA-PCR, RNA in situ hybridization, and fluorescence in situ hybridization (FISH) of metaphase chromosomes and interphase nuclei, and immunohistochemical detection of the 80 kilodalton protein (p80) derived from the NPM-ALK fusion have enabled surveys of normal and lymphoma tissues for evidence of the translocation. These studies suggest that expression of ALK protein, a novel orphan receptor tyrosine kinase, is normally confined to the nervous system. In lymphoma, NPM-ALK expression is most often seen in young patients with the monomorphic or small-cell variant of ALCL who present with advanced stage disease and have tumors with a CD30+, T- or null-cell phenotype. It is less frequently detected in older patients and in ALCL of pleomorphic histology. In addition, expression of NPM-ALK has been found in occasional CD30 negative B-cell lymphomas with diffuse large cell or immunoblastic histology. NPM-ALK is rarely, if ever, detected in Hodgkin's disease or secondary ALCL. Although initially found in primary nodal ALCL, recent studies suggest that NPM-ALK expression may occur in lymphoma at extranodal sites, including the skin; it remains controversial, however, whether CD30+ primary cutaneous lymphoma and its benign counterpart, lymphomatoid papulosis (LyP), express NPM-ALK in some cases. A retrospective study has suggested that expression of NPM-ALK is associated with a better overall 5-year survival; these results must be confirmed in prospective studies of patients with uniform staging and therapy to more fully understand the clinical significance of the t(2;5) and its novel chimeric protein, NPM-ALK.
一种复发性、相互平衡易位，即t(2;5)(p23;q35)，已在CD30+间变性大细胞淋巴瘤（ALCL）中被识别出来，ALCL是一种新识别的亚型，约占所有非霍奇金淋巴瘤（NHL）的5%。这种易位产生一种新的融合蛋白NPM-ALK，它在体外具有转化特性，当转染到小鼠骨髓中时可在体内引发大细胞淋巴瘤。多种技术，包括对NPM-ALK融合转录本进行逆转录聚合酶链反应（RT-PCR）扩增、基因组DNA-PCR、RNA原位杂交以及中期染色体和间期核的荧光原位杂交（FISH），还有对源自NPM-ALK融合的80千道尔顿蛋白（p80）进行免疫组织化学检测，这些技术可用于检测正常组织和淋巴瘤组织中是否存在这种易位。这些研究表明，ALK蛋白（一种新的孤儿受体酪氨酸激酶）的表达通常局限于神经系统。在淋巴瘤中，NPM-ALK表达最常见于患有ALCL单形性或小细胞变异型的年轻患者，这些患者呈现晚期疾病，肿瘤具有CD30+、T细胞或无细胞表型。在老年患者以及多形性组织学的ALCL中较少检测到。此外，在偶尔的具有弥漫性大细胞或免疫母细胞组织学的CD30阴性B细胞淋巴瘤中也发现了NPM-ALK的表达。在霍奇金病或继发性ALCL中极少检测到NPM-ALK。虽然最初在原发性淋巴结ALCL中发现，但最近的研究表明，NPM-ALK表达可能出现在结外部位的淋巴瘤中，包括皮肤；然而，CD30+原发性皮肤淋巴瘤及其良性对应物淋巴瘤样丘疹病（LyP）在某些情况下是否表达NPM-ALK仍存在争议。一项回顾性研究表明，NPM-ALK的表达与较好的5年总生存率相关；这些结果必须在前瞻性研究中对分期和治疗一致的患者进行验证，以更全面地了解t(2;5)及其新的嵌合蛋白NPM-ALK的临床意义。
