Identify hematopoietic stem cell intrinsic and extrinsic mechanisms, the later induced by mesenchymal stem cells, which promote transformation of MDS to AML by integrating genome-wide genomic and transcriptomic approaches in patients with MDS and AML, Examine if similar molecular events are observed in disease initiating pre-MDS stem cells and how they affect transformation to malignant cells. , Characterize the molecular nature of the cross-talk pathways between leukemia stem cells and mesenchymal stem cells or osteoblasts that affect engraftment and progression of AML. Use this knowledge to delineate the expression of novel markers of interest in MDS/AML cells and stromal cells from MDS and AML patients. , Use specific AML models to study how leukemia stem cells remodel mesenchymal stem cells to promote their engraftment and proliferation., Trace the identity of stoma cells and how their functions change during MDS development and transformation to AML., Test therapeutic approaches targeting pathways emanating from the stroma cells and influencing disease progression.