Britos-Bray M, Sacchi N, Friedman A D
Johns Hopkins Oncology Center, Division of Pediatric Oncology, Baltimore, MD 21287, USA.
Leukemia. 1996 Jun;10(6):984-90.
Truncated AML1 proteins are predicted to be expressed from out-of-frame AML1 transcripts present in myeloid leukemia cells harboring t(8;21) and t(3;21). To test whether these proteins, consisting of almost exclusively an N-terminal AML1 DNA-binding domain, interfere with myeloid differentiation we expressed a similar truncated AML1 protein in 32D cl3 myeloid cells. In all clones examined, the ectopically expressed truncated AML1 protein prevented binding of endogenous PEBP2/CBFs to DNA, possibly by interacting with all available CBF beta subunits. However, compared to control clones, the 32D cl3 clones expressing truncated AML1 remained IL-3 dependent for survival, proliferated similarly in low and high concentrations of IL-3, and differentiated similarly upon transfer to G-CSF. Thus, truncated AML1 proteins may contribute to myeloid leukemogeneis by inhibiting PEBP2/CBF activities, although contributions from other oncoproteins are likely required as well.
截短的AML1蛋白预计由存在于携带t(8;21)和t(3;21)的髓系白血病细胞中的框外AML1转录本表达。为了测试这些几乎仅由N端AML1 DNA结合域组成的蛋白是否干扰髓系分化，我们在32D cl3髓系细胞中表达了一种类似的截短AML1蛋白。在所有检测的克隆中，异位表达的截短AML1蛋白可能通过与所有可用的CBFβ亚基相互作用，阻止内源性PEBP2/CBF与DNA结合。然而，与对照克隆相比，表达截短AML1的32D cl3克隆在生存上仍依赖IL-3，在低浓度和高浓度IL-3中增殖相似，并且在转移到G-CSF后分化相似。因此，截短的AML1蛋白可能通过抑制PEBP2/CBF活性促进髓系白血病发生，尽管可能也需要其他癌蛋白的作用。
