The Role of theMLL Gene in Infant Leukemia
- 107 Downloads
TheMLL gene is a major player in leukemia, particularly in infant leukemia and in secondary, therapy-related acute leukemia. The normalMLL gene plays a key role in developmental regulation of gene expression (includingHOX genes), and in leukemia this function is subverted by breakage, recombination, and chimeric fusion with one of 40 or more alternative partner genes. In infant leukemias, the chromosome translocations involvingMLL arise during fetal hematopoiesis, possibly in a primitive lymphomyeloid stem cell. In general, these leukemias have a very poor prognosis. The malignancy of these leukemias is all the more dramatic considering their very short preclinical natural history or latency. These data raise fundamental issues of how such divergentMLL chimeric genes transform cells, why they so rapidly evolve to a malignant status, and what alternative or novel therapeutic strategies might be considered. We review here progress in tackling these questions.