title: p27(KIP1) and PTEN cooperate in myeloproliferative neoplasm tumor suppression in mice.
abstract: PTEN acts as a phosphatase for PIP3 and negatively regulates the PI3K/AKT pathway, and p27(KIP1) is a cyclin-dependent kinase inhibitor that regulates the G1 to S-phase transition by binding to and regulating the activity of cyclin-dependent kinases. Genetic alterations of PTEN or CDKN1B (p27(KIP1)) are common in hematological malignancies. To better understand how mutations in these two genes might cooperate in leukemogenesis, we inactivated both genes in the hematological compartment in mice. Here, we show that the combined inactivation of Pten and Cdkn1b results in a more severe myeloproliferative neoplasm phenotype associated with lower hemoglobin, enlarged spleen and liver, and shorter lifespan compared to inactivation of Pten alone. More severe anemia and increased myeloid infiltration and destruction of the spleen contributed to the earlier death of these mice, and elevated p-AKT, cyclin D1, and cyclin D3 might contribute to the development of this phenotype. In conclusion, PTEN and p27(KIP1) cooperate in tumor suppression in the hematological compartment.
authors.affiliation: Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden ; Laboratory of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: Jingchen
authors.initials: J
authors.lastname: Shao
authors.affiliation: Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden ; Laboratory of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: Susann
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden ; Laboratory of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Palmqvist
authors.affiliation: Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden ; Laboratory of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: Linda
authors.initials: L
authors.lastname: Fogelstrand
authors.affiliation: Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden ; Section for Haematology and Coagulation, Department of Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: Stella Y
authors.initials: SY
authors.lastname: Wei
authors.affiliation: Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Kiran
authors.initials: K
authors.lastname: Busayavalasa
authors.affiliation: Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Kui
authors.initials: K
authors.lastname: Liu
authors.affiliation: Department of Clinical Chemistry and Transfusion Medicine, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden ; Laboratory of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: Viktor M
authors.identifier: 0000-0003-2865-034X
authors.initials: VM
authors.lastname: Liu
keywords: Myeloproliferative neoplasms; PTEN; p27KIP1