PROJECT SUMMARY Blood cancers afflict children and adults and are life-threatening. The Hematologic Malignancies (HM) Program is dedicated to understanding the causes of blood cancers and developing successful gene, drug, and cellular treatment options to improve the quality of life and survival of patients. These goals are accomplished through four major aims: 1) create a deeper understanding of the biologic basis of hematological malignancies; 2) enhance our knowledge of hematopoietic stem cell (HSC) biology and our capabilities for gene therapy of hematological malignancies; 3) develop novel non-transplant treatments; and 4) improve the availability, safety, and efficacy of hematopoietic cell transplantation. These complementary and intersecting aims bring together multidisciplinary expertise in hematology, immunology, genomics, clinical trial design/implementation, computation, and biostatistics. Synergy across the research aims is achieved through close collaborations with patients and providers, interactions with COE, CRTEC, and PED, and a well-integrated network of clinical and research faculty. The HM Program currently has 105 members from all three Consortium institutions. Broad expertise of clinicians and clinical and basic scientists provide a deep skill set to successfully accomplish the program’s aims. The scientific goals are supported by the complementary expertise of Program Co-Leaders Dr. Fred Appelbaum (non-transplant) and Dr. Effie Petersdorf (transplant) and by Associate Program Leaders Dr. Janis Abkowitz (leukemia biology) and Dr. Hans-Peter Kiem (gene therapy). The structural organization of faculty with a disease (adult leukemia; pediatric leukemia; myeloma; myelodysplasia; lymphoma) and research (myeloid stem cell biology; gene therapy; radio-immunotherapy; hematopoietic cell transplantation; long-term follow-up) focus enhances collaborations within and across the program. Program members currently have $38.7M in research funding of which $12