Nosaka T, Kita K, Miwa H, Kawakami K, Ikeda T, Ohno T, Matsuoka N, Arita Y, Doi S, Nishikori M
Institute for Virus Research, Kyoto University, Japan.
Blood. 1989 Jul;74(1):361-8.
Gene configurations of immunoglobulin (Ig), T-cell antigen receptor (TCR) beta chain, and T-cell rearranging gene gamma (TRG gamma) were studied in human B-precursor lymphoblastic leukemic cells. These cells were phenotypically classified into three developmental stages (stages II through IV) according to Nadler's criteria. All of them showed the Ig heavy chain (IgH) gene rearrangement, and 67% of the cells in stage IV had the rearranged TRG gamma, albeit seldom in other stages. We further analyzed IgH gene rearrangements in detail using upstream to DH (diversity region of IgH) region probe to distinguish DJ from V-DJ recombination. All dual genotyped cells in each stage except one case in stage II showed the V-DJ rearrangements. This suggests the cross-lineage involvement of the putative recombinase, particularly in the process of V-DJ rearrangements. We next examined the transcriptional status of Ig genes as an indirect reflection of the accessibility of these genes to the recombinase. Properly spliced IgH transcripts of normal size were observed in stage IV and surface Ig positive stage, but not in stage II nor III. However, IgH transcripts of aberrant sizes were seen in stage II, III, and also IV. Cross-lineage gene rearrangements were shown to occur frequently when normally spliced IgH gene begins to be transcribed or just before this. These findings may implicate that V-DJ or V-VDJ gene rearrangements forming functional IgH genes, induce frequently TCR or TRG gene rearrangements. We propose these dual genotypes are different in origin from those observed in stem cell leukemia.
在人B前体淋巴细胞白血病细胞中研究了免疫球蛋白（Ig）、T细胞抗原受体（TCR）β链和T细胞重排基因γ（TRGγ）的基因构型。根据Nadler标准，这些细胞在表型上被分为三个发育阶段（II至IV期）。所有细胞均显示Ig重链（IgH）基因重排，IV期67%的细胞有重排的TRGγ，而其他阶段很少见。我们进一步使用IgH上游至DH（IgH多样性区域）区域探针详细分析IgH基因重排，以区分DJ与V-DJ重组。除II期1例病例外，每个阶段的所有双基因型细胞均显示V-DJ重排。这表明推定的重组酶存在跨谱系参与，特别是在V-DJ重排过程中。接下来，我们检查了Ig基因的转录状态，作为这些基因对重组酶可及性的间接反映。在IV期和表面Ig阳性阶段观察到正常大小的正确剪接的IgH转录本，但在II期和III期未观察到。然而，在II期、III期和IV期均可见异常大小的IgH转录本。当正常剪接的IgH基因开始转录时或在此之前，跨谱系基因重排频繁发生。这些发现可能意味着形成功能性IgH基因的V-DJ或V-VDJ基因重排经常诱导TCR或TRG基因重排。我们提出这些双基因型在起源上与干细胞白血病中观察到的不同。
