In this project, our team proposes to genetically engineer human iPS cells to express MLL-Af4. We will then introduce clinically identified genomic variants using CRISPR, differentiate the cells to CD34+ hematopoietic stem cell precursors, and xenograft into immunodeficient mice. We will assess the cells for clonal outgrowth, serial proliferative capacity, cell surface marker expression, latency of onset and morphologic phenotype of leukemia in xenografts.