Somatic Hypermutations in the VH Segment of Immunoglobulin Genes of CDS‐positive Diffuse Large B‐Cell Lymphomas

Somatic Hypermutations in the VH Segment of Immunoglobulin Genes of CDS‐positive Diffuse Large B‐Cell Lymphomas
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CDS 阳性弥漫性大 B 细胞淋巴瘤免疫球蛋白基因 VH 片段的体细胞高突变

DOI:
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发表时间:
1997
期刊:
Japanese journal of cancer research : Gann
影响因子:
--
通讯作者:
M. Seto
M. Seto
中科院分区:
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文献类型:
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作者:
M. Kume;R. Suzuki;Y. Yatabe;Y. Kagami;I. Miura;A. Miura;Y. Morishima;S. Nakamura;M. Seto

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目前CDS阳性(CD 5+)弥漫性大B细胞淋巴瘤(DLBL)已被确定为一个具有独特临床病理和基因型特征的同质亚组,但其起源仍有待阐明。先前通过免疫球蛋白重链可变区(VH)序列分析进行的研究表明,与大多数DLBL的GC后阶段相比,CDS 5 B-细胞恶性肿瘤(如套细胞淋巴瘤(MCL)和B-细胞慢性淋巴细胞白血病(B-CLL)细胞代表生殖中心前(pre-GC)阶段B细胞,后者显示VH基因的体细胞超突变。在本研究中,我们研究了原发性CD 5 + DLBL的VH序列,以阐明CD 5 + DLBL是否代表GC前阶段(如其他CD 5 + B细胞恶性肿瘤)或GC后阶段(如DLBL典型)。我们检查的所有8例病例(4例CDS 4 DLBL和4例CDS阴性(CD 5 −)DLBL)均显示VH节段的体细胞高突变,2例CD 5 − DLBL病例显示克隆内多样性,表明CD 5 + DLBL与CD 5 − DLBL来自相同的成熟阶段,但与B-CLL和MCL的其他惰性CD 5 + B-细胞淋巴瘤不同。这些数据表明,新生CD 5 + DLBL不仅与B-CLL和MCL属于连续谱,而且代表了弥漫性大B-细胞淋巴瘤诊断框架内的生物学不同变体。
De now CDS‐positive (CD5+) diffuse large B‐cell lymphoma (DLBL) has recently been identified as constituting a homogeneous subgroup with distinct clinicopathologic and genotypic characteristics, but its origin remains to he elucidated. Previous studies by sequence analysis of the variable region of the immunoglobulin heavy chain (VH) have shown that CDS5 B‐cell malignancies such as mantle cell lymphoma (MCL) and B‐cell chronic lymphocytic leukemia (B‐CLL) cells represent pre‐geminal center (pre‐GC) stage B cells in contrast with the post‐GC stage of most DLBLs, which show somatic hyper mutations in VH genes. In the present study, we investigated the VH sequence of de novo CD5+ DLBL to clarify whether CD5+ DLBL represents the pre‐GC stage, as do other CD5+ B‐cell malignancies, or the post‐GC stage, as is typical of DLBL. All eight cases (four CDS4 DLBL and four CDS‐negative (CD5−) DLBL) examined by us showed somatic hypermutatiohs in the VH segment and two of the CD5− DLBL cases showed intra‐clonal diversity, suggesting that CD5+ DLBLs were derived from the same maturation stage as CD5− DLBL, but were distinct from the other indolent CD5+ B‐cell lymphomas of B‐CLL and MCL. These data suggest that de novo CD5+ DLBLs do not merely lie within a continuous spectrum with B‐CLL and MCL, but represent a biologically distinct variant within the diagnostic framework of diffuse large B‐cell lymphoma.
DOI: 10.1016/0167-5699(94)90175-9
发表时间: 1994-08-01
期刊: IMMUNOLOGY TODAY
影响因子: --
作者:
CHANG, B;CASALI, P
通讯作者: CASALI, P
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DOI: --
发表时间: 1992
期刊: Oncogene
影响因子: 8
作者:
Seto,M;Yamamoto,K;Iida,S;Akao,Y;Utsumi,KR;Kubonishi,I;Miyoshi,I;Ohtsuki,T;Yawata,Y;Namba,M
通讯作者: Namba,M