Department of Clinical Medicine, University of Milano-Bicocca, Monza, Italy.
Leukemia. 2010 Aug;24(8):1445-9. doi: 10.1038/leu.2010.101. Epub 2010 Jun 3.
Chronic myeloid leukemia (CML) is caused by the BCR-ABL hybrid gene. The molecular mechanisms leading from chronic phase (CP) to blast crisis (BC) are not understood. However, both the presence and the levels of BCR-ABL seem to be important for CML progression. BCR-ABL is under the transcriptional control of BCR promoter. Here we focused on the gene expression control of BCR and BCR-ABL upon myeloid differentiation in healthy donors (HDs), CP and BC patients. As previously reported, BCR-ABL is downregulated during myeloid maturation in CP patients. A similar pattern was detected for BCR (but not for ABL) in CP-CML and in HD, thus suggesting that the two genes may be under a similar transcriptional control. In BC this mechanism is similarly impaired for both BCR-ABL and BCR. These data indicate the presence of an 'in trans' deregulated transcription of both BCR and BCR-ABL promoters, associated with CML progression.
慢性髓性白血病（CML）是由 BCR-ABL 融合基因引起的。导致慢性期（CP）向急变期（BC）的分子机制尚不清楚。然而，BCR-ABL 的存在和水平似乎对 CML 的进展都很重要。BCR-ABL 受 BCR 启动子的转录调控。在这里，我们专注于健康供体（HD）、CP 和 BC 患者的髓系分化过程中 BCR 和 BCR-ABL 的基因表达调控。如前所述，BCR-ABL 在 CP 患者的髓系成熟过程中下调。在 CP-CML 和 HD 中也检测到了 BCR 的类似模式（但 ABL 没有），这表明这两个基因可能受到类似的转录调控。在 BC 中，这种机制对于 BCR-ABL 和 BCR 同样受损。这些数据表明，存在一种“反式”的 BCR 和 BCR-ABL 启动子转录失调，与 CML 的进展相关。
