Coyle L A, Papaioannou M, Yaxley J C, Chim J S, Attard M, Hoffbrand A V, Foroni L
Department of Haematology, Royal Free Hospital School of Medicine, London.
Br J Haematol. 1996 Sep;94(4):685-93. doi: 10.1046/j.1365-2141.1996.d01-1851.x.
Immunoglobulin heavy chain gene (IgH gene) rearrangements are found in the majority of cases of B-lineage acute lymphoblastic leukaemia (ALL). We have examined bone marrow samples taken at presentation or relapse from 109 patients (79 adults and 30 children) and have performed sequence analysis of the complementarity determining region 3 (CDR3) on 65 alleles from 54 patients. We aimed to define immunoglobulin heavy chain (IgH) variable segment family use and investigate biological and structural features of the B cell in adult and childhood ALL. Using the FR1 fingerprinting method, a rearranged band was identified in 70 (89%) of 79 adult ALL and in 29 (97%) of 30 childhood ALL. This study found no preferential use or selection of IgH VH genes and no statistically significant structural differences between normal and leukaemic B cells in either adult and childhood ALL. An equal proportion of amplifiable cases of adult and childhood ALL uses more than one VH family gene (24/70, 34%, and 8/29, 27.5%, respectively). There were no significant differences in the structure or size of the CDR3 region and the variable (V) or joining (J) segment use in ALL patients compared to normal B cells. We observed that the N2 region was shorter than N1 in children whereas the opposite was observed in adults (not statistically significant). The J4 segment was a more common rearrangement in children than in adults, and in both groups J4 was more frequently associated with multiple D segment VDJ rearrangements. An increase in VH6 use in leukaemic alleles compared to normal B lymphocytes (2%) was observed but it was not statistically significant in our group of patients. Amongst children and adults, in-frame CDR3 junctions occurred in 78% and 64% of rearranged alleles, respectively, compared to 75% of in-frame sequences reported by others to occur among normal B cells.
免疫球蛋白重链基因（IgH基因）重排在大多数B系急性淋巴细胞白血病（ALL）病例中均可发现。我们检测了109例患者（79例成人和30例儿童）初诊或复发时采集的骨髓样本，并对54例患者的65个等位基因的互补决定区3（CDR3）进行了序列分析。我们旨在确定免疫球蛋白重链（IgH）可变区家族的使用情况，并研究成人和儿童ALL中B细胞的生物学和结构特征。使用FR1指纹法，在79例成人ALL中的70例（89%）和30例儿童ALL中的29例（97%）中鉴定出重排条带。本研究发现，在成人和儿童ALL中，IgH VH基因均无优先使用或选择情况，正常B细胞与白血病B细胞之间在结构上无统计学显著差异。成人和儿童ALL中可扩增病例使用一种以上VH家族基因的比例相同（分别为24/70，34%和8/29，27.5%）。与正常B细胞相比，ALL患者的CDR3区域结构或大小以及可变（V）区或连接（J）区的使用情况均无显著差异。我们观察到，儿童的N2区域比N1区域短，而在成人中则相反（无统计学显著性）。J4片段在儿童中比在成人中更常见，且在两组中J4更常与多个D片段VDJ重排相关。与正常B淋巴细胞相比，白血病等位基因中VH6的使用增加（2%），但在我们的患者组中无统计学显著性。在儿童和成人中，分别有78%和64%的重排等位基因发生读框内CDR3连接，而其他人报道正常B细胞中读框内序列的发生率为75%。
