CHARACTERIZATION OF THE NOVEL LEUKEMIA-INDUCING GENE MLF1

所有循环中的血细胞(包括红血球和白血球)都来自成人骨髓中发现的造血干细胞。干细胞逐渐发育成一种细胞类型。一旦它们沿着特定的途径开始，它们就不再产生另一种途径的细胞(例如，一旦干细胞开始发育成红细胞，它们就不会变成白细胞)。然而，也有一些成熟细胞改变了途径的例子。我们产生了一种红细胞系，当在压力条件下生长时，它有时会变成巨噬细胞(白血球)。利用这些细胞，我们鉴定了一个基因，HLS7，它与巨噬细胞的变化有关。一个美国研究小组独立地证明了这种基因可以导致白血病(血癌)。我们已经证明，HLS7对正常的血液发育有显著的影响，与它对白血病的影响一起，证明了它对血液系统的重要性。通过我们对HLS7作用机制的研究，我们发现了另一个基因MADM，它可能是HLS7的重要调节基因。我们计划研究HLS7的正常功能，它如何与MADM相互作用，以及它是如何导致白血病的。对这些基因的分析将进一步加深我们对血细胞发育和癌症形成领域的了解。

All of the circulating blood cells (including red cells and white cells) arise from haemopoietic stem cells found in the adult bone marrow. Stem cells gradually develop into one cell type. Once they have started down a particular pathway, they no longer generate cells of another pathway (e.g. once a stem cell begins to develop into red blood cells, they do not change into white cells). However, there are a few examples of mature cells that have changed pathways. We generated a red blood cell line, which has on occasions changed into macrophages (white blood cells) when grown under stressful conditions. Using these cells, we identified a gene, HLS7, which was involved in the change to macrophages. An American group has independently shown this gene can cause leukemia (blood cancer). We have shown HLS7 has dramatic effects on normal blood development and, together with its effect on leukemias, demonstrates its importance to the blood system. Through our studies on how HLS7 works, we have identified another gene, Madm, which may be an important regulator of HLS7. We plan to investigate the normal function of HLS7, how it interacts with Madm and how it causes leukemias. Analysis of these genes will further our knowledge in this field of blood cell development and cancer formation.