I am engaged in developmental therapeutics for patients with bone marrow stem cell disorders including the acute leukemias, myelodysplasia, and the myeloproliferative disorders. The areas of differentiation-based therapy, as well as cell signal modicifcation therapy (kinase inhibitors) currently with agents which act on protein kinase-C and immunologically-based therapy involving transduction of pro-inflammatory genes into leukemia cells and dendritic cell/leukemia cell fusions, represent an important current translocational focus. From a clinical standpoint we are involved in several large trials designed to improve the care of patients with acute leukemia: including immunotherapy with IL-2 as late post-remission therapy for the adults with AML (CALGB) and use of a bcl-2 antisense oligonucleotide in older adults with AmL (CALGB). We are also testing the feasibility of adding a FLT3 inhibitor to chemotherapy in newly dignosed patietns with AML and using a pediatric-like regimen to treat adults with ALL.We also have protocols employing novel agents in AML and MDS including:troxacitibine, cloretazine, gefitnib, and gamma secretase inhibitors. We also continue to be heavily involved with clinico-genetic correlates such as our work describing the frequency of JAK2 mutations in the myeloproliferative disorders and the pathophysiological significance or FIP1L1-PDGFRA fusions in the hypereosinophilic syndrome.