Overactivation of b-catenin signaling in osteoblasts affects the maturation of hematopoietic stem cells resulting in accumulation of myeloid lineage precursors cells and the development of acute myeloid leukemia. This pathway is active in 38% of AML patients. However, the cause of its activation is not yet known. Here, we hypothesize that mutations within the osteoblasts drive activated b-catenin signaling as this pathway remains active in isolated osteoblasts grown in culture for several days, suggesting that factors intrinsic to the cells are responsible for overactivation of b-catenin. To test this hypothesis, we will screen for genomic alterations in key genes affecting b-catenin activity by Sanger-based sequence analysis in osteoblasts collected from AML patients as well as healthy controls.