Mechanisms of LYL1-associated T-ALL development

T-cell ALL is among the most frequent of child-hood leukemias, and a significant sub-set of patients are not effectively treated by conventional therapies.  A subset of T-ALL with a particularly poor prognosis is associated with over-expression of the LYL1 gene, however, the role of LYL1 has been little studied.  In this project, we propose to study the role of LYL1 in T-ALL.  We have found that mice that lack the mouse Lyl1 gene show defective development of T-cells, which are the precursors of T-ALL leukemia.  We also found that when we forced Lyl1 to be expressed, we generated more T-cells.  This has led us to hypothesize that Lyl1 plays a key role in generating the T-ALL precursor cells, when LYL1 is inappropriately expressed in patients. We are proposing to study what happens to T-cells when they express excessive Lyl1.  We expect they more frequently travel to the thymus where they then expand inappropriately.  We will examine this in normal cells and also when we induce a malignancy in mice.  We will also examine the mechanism through which Lyl1 exerts its effects, with the hope that we can develop strategies to interfere with the role of Lyl1 in malignancy development.