CHARACTERIZATION OF THE NOVEL LEUKEMIA-INDUCING GENE MLF1

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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.