CD5-EXPRESSING B-CELL NON-HODGKINS-LYMPHOMAS WITH BCL-1 GENE REARRANGEMENT HAVE A RELATIVELY HOMOGENEOUS IMMUNOPHENOTYPE AND ARE ASSOCIATED WITH AN OVERALL POOR-PROGNOSIS
CD5-EXPRESSING B-CELL NON-HODGKINS-LYMPHOMAS WITH BCL-1 GENE REARRANGEMENT HAVE A RELATIVELY HOMOGENEOUS IMMUNOPHENOTYPE AND ARE ASSOCIATED WITH AN OVERALL POOR-PROGNOSIS
复制标题
DOI：
10.1182/blood.v85.6.1570.bloodjournal8561570
复制
发表时间：
1995-03-15
期刊：
影响因子：
20.3
通讯作者：
BRAYLAN, RC
中科院分区：
文献类型：
--
作者：
SEGAL, GH;MASIH, AS;BRAYLAN, RC
套细胞淋巴瘤（MCL）是典型的表达CD 5的B细胞非霍奇金淋巴瘤（NHL），经常携带染色体易位t（11;14）或bcl-1基因重排。关于严格表征的MCL的生物学特征和临床行为的数据不足。由于这些NHL已被报道表现出不同的组织学和细胞学表达，为了避免使用有点武断和主观的形态学定义，我们选择研究的情况下，MCL选择更客观的理由。具体而言，包括15个样本（来自14名患者）的CDS表达B细胞NHL与可检测的bcl-1基因重排。总体而言，这些患者的临床表现相对一致。大多数是老年男性（平均年龄67岁），表现为淋巴结病、高分期疾病和骨髓受累。除两名患者外，所有患者均复发，表现出残留肿瘤，或在对各种治疗的初始反应后出现疾病进展。9名患者死亡;这些患者的中位生存期仅为19个月。所有病例均可归类于先前描述的MCL的广泛形态学谱内，未观察到主要的组织学亚型。然而，根据组织结构，病例可分为两大组：一组为单纯弥漫型，另一组至少具有局灶性结节成分。单纯弥漫性肿瘤患者的生存率（0%）低于具有结节成分的肿瘤患者（62%生存率）。与形态学变异相反，这些NHL表现出相当均一的免疫表型模式。所有病例均表现出强烈的CD 20表达，典型的IgM和轻链表达强烈，IgD表达相对较弱。在任何情况下，CD 10检测肿瘤细胞。DNA含量分析显示非整倍体只有在三种情况下，和两组的情况下，可以任意定义的基础上，他们的S-期分数。观察到纯扩散生长模式和高S相分数（大于5%）之间的关系。正如从这种关联中所预期的那样，具有高S期分数的肿瘤患者（14%存活率）比具有低S期分数的肿瘤患者（57%存活率）表现更差。12例患者的13个NHL在主要易位簇（MTC）处有可证实的bcl-1基因重排。bcl-1断裂点聚集在MTC的63-bp区域内，并且来自每个患者的扩增的肿瘤DNA具有独特的N-核苷酸连接序列和Ig连接区断裂点位点。另外两个NHL仅通过Southern印迹杂交检测到bcl-1基因重排，该杂交使用基因组探针针对远离MTC的断点位点。我们的结论是，表达CD 5的B细胞NHL与bcl-1基因重排，可以在形态学上归类为MCL，具有相对统一的免疫表型特征，并与整体预后不良。结构生长模式和动力学信息，如S期分数，可能有助于将这些NHL中更具侵袭性的一组与相对侵袭性较低的亚组分开。(C)1995年，美国血液学会。
Mantle cell lymphomas (MCLs) are typically CD5-expressing B-cell non-Hodgkin's lymphomas (NHLs) that frequently harbor the chromosomal translocation t(11;14) or bcl-1 gene rearrangements. Insufficient data are available on the biologic features and clinical behavior of rigorously characterized MCL. As these NHLs have been reported to exhibit various histologic and cytologic expressions, and in order to avoid using somewhat arbitrary and subjective morphologic definitions, we chose to study cases of MCL selected on more objective grounds. Specifically, 15 samples (from 14 patients) of CDS-expressing B-cell NHLs with detectable bcl-1 gene rearrangement were included. Overall, these patients had relatively uniform clinical manifestations. Most were older men (mean age, 67 years) who presented with lymphadenopathy, high-stage disease, and bone marrow involvement. All but two patients relapsed, demonstrated residual tumor, or had disease progression after an initial response to various therapies. Nine patients have died; these patients had a median survival of only 19 months. All cases could be classified within the broad morphologic spectrum previously described for MCL, and no predominant histologic subtype was observed. However, cases could be segregated into two major groups according to tissue architecture: one with a purely diffuse pattern and the other with at least a focal nodular component. Patients with purely diffuse tumors had a lower survival rate (0%) than those with tumors having a nodular component (62% survival rate). In contrast to the morphologic variability, these NHL exhibited a rather homogeneous immunophenotypic pattern. All cases demonstrated intense CD20 expression, with typically intense IgM and light chain expression, and relatively weak IgD expression. In no case was CD10 detected on the neoplastic cells. DNA content analysis showed aneuploidy only in three instances, and two groups of cases could be arbitrarily defined on the basis of their S-phase fraction. A relationship between a purely diffuse growth pattern and a high S-phase fraction (greater than 5%) was observed. As expected from this association, patients with tumors having high S-phase fractions fared worse (14% survival rate) than those patients with tumors showing lower S phase fractions (57% survival rate). Thirteen NHLs from 12 patients had amplifiable bcl-1 gene rearrangements at the major translocation cluster (MTC). The bcl-1 breakpoints aggregated within a 63-bp region of the MTC, and the amplified tumor DNA from each patient had unique N-nucleotide junctional sequences and lg joining region breakpoint sites. Two additional NHLs had bcl-1 gene rearrangements detected only with Southern blot hybridization using a genomic probe directed at a breakpoint site distant from the MTC. We conclude that CD5-expressing B-cell NHLs with bcl-1 gene rearrangement can be morphologically classified as MCL, have relatively uniform immuno-phenotypic characteristics, and are associated with an overall poor prognosis. Architectural growth pattern and kinetic information, such as S-phase fraction, may help separate a more aggressive group of these NHL from a relatively less aggressive subset. (C) 1995 by The American Society of Hematology.