Greaves M F, Chan L C, Furley A J, Watt S M, Molgaard H V
Blood. 1986 Jan;67(1):1-11.
An increasing number of reports document instances in which individual leukemic cells coexpress markers normally believed to be restricted to a single lineage. This has been interpreted by McCulloch and colleagues as aberrant programming or lineage infidelity and contrasts with earlier suggestions that lineage fidelity of gene expression was usually maintained in leukemia. We argue that several examples of infidelity are suspect on technical grounds, whereas others are bona fide and require explanation, eg, partial rearrangements and expression of Ig heavy-chain and/or T cell receptor genes in inappropriate cells and terminal deoxynucleotidyl transferase in leukemic myeloblasts. Individual examples of truly aberrant gene expression may well occur in leukemia but with insufficient regularity to be of general significance. We suggest that verifiable and consistent examples of apparent lineage infidelity do not reflect genetic misprogramming but rather the existence of a transient phase of limited promiscuity of gene expression occurring in normal biopotential or multipotential progenitors and able to be preserved as a relic in leukemic blast cell populations that are in maturation arrest. This alternative explanation has interesting implications for mechanisms of hematopoietic differentiation and leads to some testable predictions.
越来越多的报告记录了个别白血病细胞共表达通常被认为仅限于单一谱系的标志物的情况。McCulloch及其同事将此解释为异常编程或谱系不忠实，这与早期关于白血病中基因表达的谱系忠实性通常得以维持的观点形成对比。我们认为，一些不忠实的例子在技术层面上值得怀疑，而其他一些则是真实存在且需要解释的，例如，不适当细胞中免疫球蛋白重链和/或T细胞受体基因的部分重排和表达，以及白血病成髓细胞中的末端脱氧核苷酸转移酶。真正异常的基因表达的个别例子很可能在白血病中出现，但频率不足以具有普遍意义。我们认为，可验证且一致的明显谱系不忠实的例子并不反映基因编程错误，而是反映了在正常双能或多能祖细胞中存在的基因表达有限混杂的短暂阶段，并且能够作为一种遗迹保留在处于成熟停滞状态的白血病母细胞群体中。这种替代性解释对造血分化机制具有有趣的启示，并导致一些可检验的预测。
