Klein G
Department of Tumor Biology, Karolinska Institutet, Stockholm, Sweden.
Princess Takamatsu Symp. 1986;17:159-70.
The regular activation of the c-myc oncogene by juxtaposition to one of the immunoglobulin loci by chromosomal translocation in Burkitt's lymphoma (BL), mouse plasmacytoma and rat immunocytoma indicates that these translocations represent an essential, i.e. rate limiting step in the development of these tumors. Since the myc-carrying chromosome appears to break at random, but preserves the integrity of the two coding exons, the exclusive involvement of myc (rather than other oncogenes) requires special comment. It must be relatable to the specific functional features of the precursor cells and to the normal role of the myc protein. Recent evidence indicates that the myc gene is regularly turned off before or at the time when the cell enters a pathway that is programmed to lead it towards a resting G0 state. Clonally expanded B-cells are believed to turn into resting memory cells upon waning of the antigenic stimulus. The normal, non-translocated myc-allele is regularly switched off in both BL and murine plasmacytoma (MPC), indicating that the cell has already obeyed a program that involves the down regulation of myc. The Ig-juxtaposed, translocated myc remains highly expressed, however, and may be responsible for keeping the cells in cycle. The possibility that BL and MPC may arise from candidate memory cells, rather than pre-B cells, is also suggested by the fact that all BL-tumors and derived lines make a heavy chain. Since the myc/Ig juxtaposition is a special case of a non-functional rearrangement, this is only expected if the precursor cell would have been preselected for a functional Ig-product. The memory cell hypothesis is further supported by the fact that the majority of BLs make IgM, most MPC make IgA and the rat immunocytomas make IgE. This could correspond to the most frequent type of the memory cell in the anatomical areas and under the physiological or pathophysiological conditions associated with the natural history of each tumor. This brief review is restricted to oncogene activation by chromosomal translocations in B-cell derived tumors.
在伯基特淋巴瘤（BL）、小鼠浆细胞瘤和大鼠免疫细胞瘤中，c-myc癌基因通过染色体易位与免疫球蛋白基因座之一并列而被定期激活，这表明这些易位是这些肿瘤发生发展中的一个关键步骤，即限速步骤。由于携带myc的染色体似乎是随机断裂的，但保留了两个编码外显子的完整性，myc（而非其他癌基因）的唯一参与需要特别说明。这一定与前体细胞的特定功能特征以及myc蛋白的正常作用有关。最近的证据表明，在细胞进入被编程引导至静止G0状态的途径之前或之时，myc基因通常会被关闭。据信，克隆扩增的B细胞在抗原刺激减弱时会转变为静止的记忆细胞。在BL和小鼠浆细胞瘤（MPC）中，正常的、未发生易位的myc等位基因通常会被关闭，这表明细胞已经遵循了一个涉及下调myc的程序。然而，与Ig并列的、发生易位的myc仍然高度表达，可能负责使细胞保持在细胞周期中。所有BL肿瘤及其衍生细胞系都产生重链这一事实也提示，BL和MPC可能起源于候选记忆细胞，而非前B细胞。由于myc/Ig并列是一种无功能重排的特殊情况，只有在前体细胞已被预先选择用于产生功能性Ig产物的情况下才会出现这种情况。记忆细胞假说进一步得到以下事实的支持：大多数BL产生IgM，大多数MPC产生IgA，大鼠免疫细胞瘤产生IgE。这可能对应于与每种肿瘤自然史相关的解剖区域以及生理或病理生理条件下最常见的记忆细胞类型。本简要综述仅限于B细胞来源肿瘤中染色体易位导致的癌基因激活。
