FREQUENT SOMATIC MUTATIONS IN D-SEGMENTS AND/OR JH-SEGMENTS OF IG GENE IN WALDENSTROMS MACROGLOBULINEMIA AND CHRONIC LYMPHOCYTIC-LEUKEMIA (CLL) WITH RICHTERS-SYNDROME BUT NOT IN COMMON CLL
FREQUENT SOMATIC MUTATIONS IN D-SEGMENTS AND/OR JH-SEGMENTS OF IG GENE IN WALDENSTROMS MACROGLOBULINEMIA AND CHRONIC LYMPHOCYTIC-LEUKEMIA (CLL) WITH RICHTERS-SYNDROME BUT NOT IN COMMON CLL
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DOI：
10.1182/blood.v85.7.1913.bloodjournal8571913
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发表时间：
1995-04-01
期刊：
影响因子：
20.3
通讯作者：
SAITO, S
中科院分区：
文献类型：
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作者：
AOKI, H;TAKISHITA, M;SAITO, S
V（D）J重组和体细胞超突变在B细胞分化期间受到发育调节;因此，lg基因的DNA分析描绘了B细胞肿瘤的细胞起源。我们分析了7例Waldenstrom巨球蛋白血症（WM）和10例慢性B细胞淋巴细胞白血病（CLL）（其中2例进展为高度非霍奇金淋巴瘤（NHL），即Richter综合征（RS））的肿瘤细胞Ig重链基因的第三互补决定区和邻近区域。在WM和CLL中均未发现VH替换或持续体细胞突变引起的克隆内变异。我们在所有WM患者和10例CLL患者中的4例（包括2例RS患者）中发现D和/或JH段替换突变。置换突变集中在JH片段的密码子102。在WM（5/7 [71.4%]）和CLL（7/10 [70.0%]）中发现优先利用JH 4基因，在CLL（5/10 [50.0%]）中发现优先利用DXP家族基因。总之，在抗原刺激和选择的影响下产生WM和CLL伴RS。然而，大多数CLL可能来自具有非突变Ig基因的限制性库的不同亚群。(C)1995年，美国血液学会。
V(D)J recombination and somatic hypermutations are developmentally regulated during B-cell differentiation; therefore, DNA analysis of the lg gene delineates the cellular origin of B-cell neoplasms. We analyzed the third complementarity-determining region and adjacent regions of the lg heavy-chain gene of tumor cells from 7 patients with Waldenstrom's macroglobulinemia (WM) and from 10 patients with B-cell chronic lymphocytic leukemia (CLL), 2 of whom progressed to high-grade non-Hodgkin's lymphoma (NHL), ie, Richter's syndrome (RS). There were no intraclonal variations resulting from VH replacements or ongoing somatic mutations in both WM and CLL, We found replacement mutations in the D and/or JH segments in all patients with WM and in 4 of the 10 patients with CLL, including the 2 RS patients. Replacement mutations were clustered in codon 102 of the JH segment. Preferential utilization of the JH4 gene was found in WM (5 of 7 [71.4%]) and in CLL (7 of 10 [70.0%]), and DXP family genes in CLL (5 of 10 [50.0%]). In conclusion, WM and CLL with RS are generated under the influence of antigenic stimulation and selection. However, the majority of CLL may arise from a distinct subpopulation that has the restricted repertoire of nonmutated lg genes. (C) 1995 by The American Society of Hematology.