IL-34 induces differentiation. IL-34 induces differentiation of normal hematopoietic/stem progenitor cells (HSPCs) as well as acute myeloid leukemia (AML) blast by binding to its previously unrecognized receptor, TREM2, instead of one of its known receptors: CSF1R, PTPz, or syndecan 1 (SDC1). Although osteoclasts likely represent an important source of IL-34 production, the sources of IL-34 production in patients with AML are unclear, as are the potential consequences of long-term IL-34 administration.