Presence of somatic hypermutation and activation-induced cytidine deaminase in acute lymphoblastic leukemia L2 with t(14;18)(q32;q21)
Presence of somatic hypermutation and activation-induced cytidine deaminase in acute lymphoblastic leukemia L2 with t(14;18)(q32;q21)
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DOI：
10.1111/j.1600-0609.2004.00338.x
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发表时间：
2005-01-01
影响因子：
3.1
通讯作者：
Takeuchi, M
中科院分区：
文献类型：
--
作者：
Hardianti, MS;Tatsumi, E;Takeuchi, M
目的：急性淋巴细胞白血病（ALL）伴L2（FAB）形态很少报告显示t（14;18）（q32;q21）。我们的目的是描述这种类型的ALL在B系分化中所处的阶段。研究方法：在3个细胞系和2个新鲜样本中，包括一对匹配的新鲜细胞和细胞系细胞，研究了免疫球蛋白重链可变区（IgV（H））基因的体细胞超突变（SHM）和末端脱氧核苷酸转移酶（TdT）、重组激活基因1和2（RAG-1和-2）以及激活诱导的胞苷脱氨酶（AID）的表达。结果：TdT、RAG-1、RAG-2在大肠杆菌中均有表达。AID在五个样品中的四个中表达。IgV（H）基因的SHM在所有样本中均存在，平均频率为11.84%，与滤泡性淋巴瘤相当。在两个新鲜样品中观察到正在进行的突变。结论：由于AID和SHM通常被认为是成熟B细胞表现出的特性，因此本研究中AID和SHM的存在似乎与B系分化中ALL早期衍生的一般理解不一致。本文的结果对疾病类型（ALL或淋巴瘤）与起源阶段之间的关系、早期表型与成熟基因组特征的重叠以及t（14;18）（q32;q21）的发生机制与引起SHM的机制之间的可能关系提供了一些见解。
Aim: Acute lymphoblastic leukemia (ALL) with L2 (FAB) morphology has rarely been reported to show t(14;18)(q32;q21). We aimed to delineate the stage at which this type of ALL is derived in B-lineage differentiation. Methods: The somatic hypermutation (SHM) of the variable region of immunoglobulin heavy chain (IgV(H)) gene and the expression of terminal deoxynucleotidyl transferase (TdT), recombination-activating gene 1 and 2 (RAG-1 and -2), and activation-induced cytidine deaminase (AID) were investigated in three cell lines and two fresh samples, including a pair of matched fresh and cell line cells. Results: TdT, RAG-1, and RAG-2 were variably expressed. AID was expressed in four of five samples. SHM of the IgV(H) gene was found in all samples with high average frequency (11.84%) comparable with that in follicular lymphoma. Ongoing mutation was seen in two fresh samples. Conclusion: As AID and SHM are generally regarded as properties exhibited by mature B cells, the presence of AID and SHM in this study seems to be incompatible with the general understanding of the early stage derivation of ALL in B-lineage differentiation. The results here give some insight into the relationship between disease type (ALL or lymphoma) and derivation stage, the overlapping of the early stage phenotype and the mature genomic characteristics, and the probable relationship between the mechanism of the occurrence of t(14;18)(q32;q21) and the machinery causing SHM.