Differential rates of somatic hypermutation in V-H genes among subsets of chronic lymphocytic leukemia defined by chromosomal abnormalities
Differential rates of somatic hypermutation in V-H genes among subsets of chronic lymphocytic leukemia defined by chromosomal abnormalities
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DOI：
10.1182/blood.v89.11.4153
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发表时间：
1997-06-01
期刊：
影响因子：
20.3
通讯作者：
Stevenson, FK
中科院分区：
文献类型：
--
作者：
Oscier, DG;Thompsett, A;Stevenson, FK
慢性淋巴细胞白血病（CLL）是一种B细胞肿瘤，涉及通常表达CD 5抗原和低水平表面IG的小淋巴细胞。在这个定义范围内，在细胞形态、核型异常和临床病程方面存在异质性。12三体是最常见的核型异常，常见于具有非典型形态学的CLL亚群中。它也与晚期疾病有关，可能与预后不太有利有关。染色体13 q14异常病例的另一个子集具有典型的淋巴细胞形态。为了评估由这两种染色体异常定义的疾病亚群中起源细胞的克隆史，我们研究了10例具有非典型形态的12三体和8例具有典型形态的13 q14异常中V-H基因的使用和体细胞突变模式。此外，还分析了4例同时伴有两种染色体异常的病例。结果证实了V（H）1家族在所有亚群中的共同使用，然而，体细胞突变的模式是不同的，12三体病例显示出最低水平的突变（平均值+/- SD，0.34% +/- 0.86%），13 q14异常病例显示出显著水平（6.5% +/- 1.67%）。4例同时存在两种异常的病例显示混合模式。所有突变病例均具有克隆内同源性，10例中有3例具有抗原选择的模式指示。这些结果表明CLL的两个子集的克隆历史可能不同。(C)1997年，美国血液学会。
Chronic lymphocytic leukemia (CLL) is a B-cell tumor involving small lymphocytes that generally express the CD5 antigen and low levels of surface Ig. Within this definition, there is heterogeneity among cases in cell morphology, karyotypic abnormalities, and clinical course. Trisomy 12, the most frequent karyotypic abnormality, is commonly found in a subset of CLL with atypical morphology. It has also been associated with advanced disease, and possibly with a less favorable prognosis. A further subset of cases with abnormalities involving chromosome 13q14 have typical lymphocyte morphology. Occasionally, the two abnormalities are found together, To assess the clonal history of the cell of origin in disease subsets defined by these two chromosomal abnormalities, we investigated the usage of V-H genes and the pattern of somatic mutation in 10 cases of trisomy 12 with atypical morphology and eight cases of 13q14 abnormality with typical morphology. In addition, four cases with both chromosomal abnormalities were analyzed. Results confirm a common usage of the V(H)1 family in all subsets, However, the patterns of somatic mutation were distinct, with cases of trisomy 12 showing a minimal level of mutation (mean +/- SD, 0.34% +/- 0.86%) and cases of 13q14 abnormality showing significant levels (6.5% +/- 1.67%). The four cases with both abnormalities showed a mixed pattern. All mutated cases had intraclonal homogeneity, and three of 10 had a pattern indicative of antigen selection, These results suggest that the clonal history of the two subsets of CLL may differ. (C) 1997 by The American Society of Hematology.