CHROMOSOME TRANSLOCATIONS AND IG GENES IN HUMAN LEUKEMIA

关于最近关于致癌机制的假设， 基因组的水平，有人认为某些染色体 在人类淋巴样肿瘤中常见的易位可能涉及 免疫球蛋白基因，并带来这些基因的转录活性部分 基因与基因组的其他片段并列(癌基因？)， 导致它们的激活和肿瘤性转化。我们现在有了 已完成的计划研究，扩展了我们之前的观察结果 更常见的8；14易位到变异型8；22和2；8易位 在伯基特淋巴瘤中。我们已经在这两个方面证明了这一点 在不同的情况下，c-myc癌基因保留在8q+染色体上， 免疫球蛋白轻链基因易位到这条8号染色体 导致c-myc癌基因转录激活。这表明 免疫球蛋白基因的激活效应是否会发生 它位于c-myc癌基因的5‘端或3’端，而且 癌基因本身的重排并不是必需的。我们现在是 将这些研究扩展到具有特征性t(11；14)的B细胞肿瘤 (q.13；q.32)和t(14；18)(q.32；q.21)染色体易位。我们的 初步结果表明，14号染色体上的断裂点涉及 免疫球蛋白重链基因，并提示到目前为止 未鉴定的原癌基因(bc1-1、bc1-2)可能从 11号和18号染色体的长臂分别与重链基因座相连 在14号染色体上，推测的原癌基因重排。 我们还证明了慢性粒细胞白血病22号染色体上的断裂点 髓性白血病(CML)位于波长恒定区的远端 轻链位置等与8；22中看到的断点不同 伯基特淋巴瘤的变种。初步数据表明，与 慢性粒细胞白血病Lamda轻链基因可能参与了慢性粒细胞白血病的发病机制。 带有费城染色体的急性淋巴细胞白血病(ALL)。(M)

In connection with recent hypotheses concerning carcinogenic mechanisms at the level of the genome, it has been suggested that certain chromosomal translocations frequently observed in human lymphoid neoplasms may involve immunoglobulin genes and bring transcriptionally active portions of these genes into juxtaposition with other segments of the genome (oncogenes?), leading to their activation and neoplastic transformation. We have now completed planned studies that extend our previous observations with the more common 8;14 translocation to the variant 8;22 and 2;8 translocations in the Burkitt lymphoma. We have demonstrated that in both of these variant circumstances, the c-myc oncogene remains on the 8q+ chromosome and that the immunoglobulin light chain gene translocates to this chromosome 8 resulting in transcriptional activation of the c-myc oncogene. This showed that the activating effect of the immunoglobulin gene could occur whether it was located on the 5' side or the 3' side of the c-myc oncogene and also that rearrangement of the oncogene itself was not required. We are now extending these studies to B-cell neoplasms with characteristic t(11;14) (q.13; q.32) and t(14;18) (q.32; q.21)chromosome translocations. Our initial results indicate that the breakpoint on chromosome 14 involves the immunoglobulin heavy chain locus, and have suggested that as yet unidentified proto-oncogenes (bc1-1, bc1-2) may be translocated from the long arms of chromosomes 11 and 18, respectively to the heavy-chain locus on chromosome 14 with rearrangement of the postulated proto-oncogenes. We\have also shown that the breakpoint on chromosome 22 in chronic myelogenous leukemia (CML) is distal to the constant region of the lambda light-chain locus and so is different from the breakpoint seen in the 8;22 variant of the Burkitt lymphoma. Preliminary data suggests that unlike CML, the lamda light-chain gene may be involved in the pathogenesis of acute lymphocytic leukemia (ALL) with the Philadelphia chromosome. (M)