The miR-17–92 microRNA cluster is frequently amplified in lymphomas and other cancers, and its miRNAs are highly expressed in cancer cells. Elevated miR-17–92 expression in lymphocytes leads to lymphoproliferative disease and autoimmunity in mice, with premature death. These mice show increased lymphocyte proliferation and reduced apoptosis. miR-17–92 miRNAs suppress tumor suppressor Pten and pro-apoptotic protein Bim, contributing to the observed disease. The study shows that miR-17–92 transgenic mice develop lymphoproliferative disease and autoimmunity, with elevated miR-17–92 expression leading to reduced Pten and Bim protein levels. These findings suggest that miR-17–92 miRNAs play a role in lymphomagenesis by suppressing tumor suppressors and promoting cell survival. The study also highlights the importance of Pten and Bim in maintaining immune tolerance and preventing autoimmunity. The results indicate that miR-17–92 overexpression contributes to lymphoma development in patients with miR-17–92 amplification. The study provides insights into the molecular mechanisms underlying miR-17–92's role in lymphomagenesis and autoimmunity.The miR-17–92 microRNA cluster is frequently amplified in lymphomas and other cancers, and its miRNAs are highly expressed in cancer cells. Elevated miR-17–92 expression in lymphocytes leads to lymphoproliferative disease and autoimmunity in mice, with premature death. These mice show increased lymphocyte proliferation and reduced apoptosis. miR-17–92 miRNAs suppress tumor suppressor Pten and pro-apoptotic protein Bim, contributing to the observed disease. The study shows that miR-17–92 transgenic mice develop lymphoproliferative disease and autoimmunity, with elevated miR-17–92 expression leading to reduced Pten and Bim protein levels. These findings suggest that miR-17–92 miRNAs play a role in lymphomagenesis by suppressing tumor suppressors and promoting cell survival. The study also highlights the importance of Pten and Bim in maintaining immune tolerance and preventing autoimmunity. The results indicate that miR-17–92 overexpression contributes to lymphoma development in patients with miR-17–92 amplification. The study provides insights into the molecular mechanisms underlying miR-17–92's role in lymphomagenesis and autoimmunity.