Lutz P G, Houzel-Charavel A, Moog-Lutz C, Cayre Y E
Unité INSERM U417, Hôpital Saint Antoine, Paris, France.
Blood. 2001 Apr 15;97(8):2449-56. doi: 10.1182/blood.v97.8.2449.
A pivotal role has been assigned to Myb in the control of myeloid cell growth. Although Myb is a target of retinoic acid, little is known about the mechanisms by which it may contribute to induced growth arrest in leukemia cells. Indeed, few Myb target genes are known to be linked to proliferation. Myeloblastin is involved in the control of proliferation in myeloid leukemia cells. It is expressed early during hematopoiesis and is a granulocyte colony-stimulating factor-responsive gene. Myeloblastin can confer factor-independent growth to hematopoietic cells, an early step in leukemia transformation. The myeloblastin promoter contains PU.1, C/EBP, and Myb binding sites, each of which are critical for constitutive expression in myeloid cells. Inhibition of myeloblastin expression in leukemia cells growth-arrested by retinoic acid is demonstrated to depend on Myb down-regulation. Myb is shown to induce myeloblastin expression and abolish its down-regulation by retinoic acid. Altogether, the data offer a clue as to how a myeloid-specific transcriptional machinery can be accessible to regulation by retinoic acid and point to myeloblastin as a novel target of Myb. This link between Myb and myeloblastin suggests a previously nonidentified Myb pathway through which growth arrest is induced by retinoic acid in myeloid leukemia cells.
Myb在髓系细胞生长控制中发挥着关键作用。尽管Myb是视黄酸的作用靶点，但对于其在白血病细胞中诱导生长停滞的机制却知之甚少。实际上，已知很少有Myb靶基因与增殖相关。成髓细胞素参与髓系白血病细胞的增殖控制。它在造血早期表达，是一种粒细胞集落刺激因子反应性基因。成髓细胞素可赋予造血细胞不依赖因子的生长能力，这是白血病转化的早期步骤。成髓细胞素启动子包含PU.1、C/EBP和Myb结合位点，其中每个位点对于髓系细胞中的组成型表达都至关重要。已证明视黄酸诱导白血病细胞生长停滞时，对成髓细胞素表达的抑制取决于Myb的下调。Myb可诱导成髓细胞素表达，并消除视黄酸对其的下调作用。总之，这些数据为视黄酸如何调控髓系特异性转录机制提供了线索，并指出成髓细胞素是Myb的一个新靶点。Myb与成髓细胞素之间的这种联系提示了一条此前未被识别的Myb途径，视黄酸通过该途径在髓系白血病细胞中诱导生长停滞。
