Hematologic Malignancies

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PROJECT SUMMARY The goal of the Hematologic Malignancies (HM) Program is to gain a better understanding of the biology underlying hematologic neoplasms and to apply this knowledge to improve the diagnosis and treatment of these disorders. In working toward this goal, we have a broad research program with major themes of mechanisms of disease pathogenesis, biomarker monitoring, and the development of new therapies. The 41 members within our program represent 7 departments within the School of Medicine and the Department of Chemistry in the School of Humanities and Sciences. They are supported by peer-reviewed research totaling $8.6M, including 9 R01s. Peer-reviewed funding consists of $4.3M from the NCI, $2.7M from other NIH institutes, and $1.6M from other sources. Our program has emphasized translational research to the clinic in diagnostics and novel therapeutics and from the clinic to the laboratory in studies of patient-derived tissues. During this CCSG cycle, 670 publications have been published in peer-reviewed journals, of which 23% were intra-programmatic, 36% were inter-programmatic, 94% were multi-institutional, and 32% were in high-impact journals (32% IF >10; 17% IF >20). During the last funding period, our members served as lead investigators for clinical trials leading to several FDA approvals, including ibrutinib for chronic graft vs. host disease and mogamulizumab and brentuximab for cutaneous T cell lymphoma. Our program members have been major contributors to the development of the anti-CD47 antibody magrolimab for hematologic malignancies and are now active participants in clinical trials for acute myeloid leukemia and myelodysplastic syndromes. Cooperative group clinical trials in chronic lymphocytic leukemia, including combination ibrutinib and venetoclax, have been led by program members. Hematologic Malignancies program members have pioneered the measurement of liquid biopsies for prognosis and tracking of diffuse large B cell lymphoma with potentially practice-changing results. Our pre-clinical and laboratory studies have advanced novel immunotherapy methods, including in situ vaccination and in vivo delivery of mRNA therapeutics that have entered early-phase clinical trials in some cases. Ongoing basic science efforts are focused on the characterization of leukemia stem cells, application of single- cell technologies to the study of disease and cellular heterogeneity, investigations into lymphomagenesis with attention to the Myc oncogene, epigenetic contributions to hematologic malignancies, and the role of the immune system in combatting these cancers. In the future, we aim to continue our efforts to develop approaches to replace current cytotoxic regimens with safer, more effective therapies for hematologic neoplasms.