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This review will discuss the biological and clinical relationship of germline mutations with clonal hematopoiesis, bone marrow microenvironment, and immunity in the progression of leukemia.Purpose of review Dipeptidyl peptidase 4 (DPP4) is a serine protease with diverse regulatory functions in healthy and diseased cells. Much remains unknown about the mechanisms and targets of DPP4. Here we discuss new studies exploring DPP4-mediated cellular regulation, provide an updated list of potential targets of DPP4, and discuss clinical implicat