In the field of pediatric cancer, leukemia (blood cancer) occurring in infants remains a considerable therapeutic challenge, with poor prognosis for survival. One of the main drivers of this type of cancer is an anomaly occurring in a gene that is essential to sustain blood cells, named Mll, also found in leukemia induced by chemotherapy agents. In the proposed studies, an emerging family of genes called histone demethylases (HD), which oppose the action of Mll, will be further studied in the blood system, given my recent findings that point to a role for these candidates in both normal blood cells and leukemia. This work aims to improve our understanding of normal blood cells, and help develop specific therapies to treat leukemia. Blood stem cells are rare, but central in sustaining the production of blood cells, as this tissue needs to be constantly replenished. They are the crucial cell type that ensures the success of bone marrow transplantation sometimes used to treat leukemia patients. Also, the concept of leukemia stem cells has recently emerged, pointing to a specific sub-group of cancer cells that have an outstanding capacity to sustain tumour avtivity. Given that the HD Jarid1b seems to oppose the role of Mll in blood stem cells in my preliminary work, the first aim of this application is to identify the specific regions of the cell nucleus that are regulated by Jarid1b. Indeeed, genetic information is stored in human cells in this structure called the nucleus. My work would contribute in deciphering the specific genetic code required for preserving stem cell identity, and aberrantly so in leukemia stem cells. The role of Jarid1b and other HD will also be validated in human cells, given our recent addition of infant leukemia samples to the Quebec Leukemia Cell Bank.