This study investigates the effects of elevated miR-17–92 expression in lymphocytes on lymphoproliferative disease and autoimmunity. Mice with increased miR-17–92 expression in lymphocytes developed lymphoproliferative disease and autoimmunity, leading to premature death. These mice showed increased proliferation and reduced activation-induced cell death in lymphocytes. miR-17–92 suppressed the expression of tumor suppressors Pten and Bim, which are crucial for maintaining central and peripheral tolerance. The downregulation of Pten and Bim contributed to the observed phenotypes, as evidenced by the similar phenotype in Pten and Bim double heterozygous mice. Additionally, elevated miR-17–92 expression enhanced the proliferation and survival of CD4+ T cells and B2 cells in vitro. The study suggests that miR-17–92 overexpression may play a role in early phases of lymphomagenesis and autoimmune diseases.This study investigates the effects of elevated miR-17–92 expression in lymphocytes on lymphoproliferative disease and autoimmunity. Mice with increased miR-17–92 expression in lymphocytes developed lymphoproliferative disease and autoimmunity, leading to premature death. These mice showed increased proliferation and reduced activation-induced cell death in lymphocytes. miR-17–92 suppressed the expression of tumor suppressors Pten and Bim, which are crucial for maintaining central and peripheral tolerance. The downregulation of Pten and Bim contributed to the observed phenotypes, as evidenced by the similar phenotype in Pten and Bim double heterozygous mice. Additionally, elevated miR-17–92 expression enhanced the proliferation and survival of CD4+ T cells and B2 cells in vitro. The study suggests that miR-17–92 overexpression may play a role in early phases of lymphomagenesis and autoimmune diseases.