title: Deletion of Pten in CD45-expressing cells leads to development of T-cell lymphoblastic lymphoma but not myeloid malignancies.
abstract: Since its discovery in the late 1990s, Pten has turned out to be one of the most important tumor suppressor genes. Pten loss results in increased activation of the phosphatidylinositol 3-kinase/Akt signaling pathway, which is associated with increased proliferation, survival, and neoplastic growth. Here, we have addressed the effects of conditional deletion of Pten in hematopoietic cells by crossing Pten conditional knockout mice with a knock-in mouse expressing the Cre recombinase in the CD45 locus. CD45 is also known as leukocyte common antigen, and it is expressed in virtually all white cells and in hematopoietic stem cells. Using a reporter mouse, we demonstrate that CD45:Cre mouse displays recombinase activity in both myeloid and lymphoid cells. However, deletion of Pten in CD45-expressing cells induces development of T-cell acute lymphoblastic leukemia and lymphoma, but not other hematologic malignancies.
authors.affiliation: Oncologic Pathology Group, Departament de Ciències Mèdiques Bàsiques, Universitat de Lleida, Hospital Universitari Arnau de Vilanova, Institut de Recerca Biomèdica de Lleida, Lleida, Spain; and.
authors.forename: Cristina
authors.initials: C
authors.lastname: Mirantes
authors.affiliation: Oncologic Pathology Group, Departament de Ciències Mèdiques Bàsiques, Universitat de Lleida, Hospital Universitari Arnau de Vilanova, Institut de Recerca Biomèdica de Lleida, Lleida, Spain; and.
authors.forename: Maria Alba
authors.initials: MA
authors.lastname: Dosil
authors.affiliation: Institute for Stem Cell Research, Medical Research Council Center for Regenerative Medicine, Edinburgh, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Hills
authors.affiliation: Institute for Stem Cell Research, Medical Research Council Center for Regenerative Medicine, Edinburgh, United Kingdom.
authors.forename: Jian
authors.initials: J
authors.lastname: Yang
authors.affiliation: Oncologic Pathology Group, Departament de Ciències Mèdiques Bàsiques, Universitat de Lleida, Hospital Universitari Arnau de Vilanova, Institut de Recerca Biomèdica de Lleida, Lleida, Spain; and.
authors.forename: Núria
authors.initials: N
authors.lastname: Eritja
authors.affiliation: Oncologic Pathology Group, Departament de Ciències Mèdiques Bàsiques, Universitat de Lleida, Hospital Universitari Arnau de Vilanova, Institut de Recerca Biomèdica de Lleida, Lleida, Spain; and.
authors.forename: Maria
authors.initials: M
authors.lastname: Santacana
authors.affiliation: Oncologic Pathology Group, Departament de Ciències Mèdiques Bàsiques, Universitat de Lleida, Hospital Universitari Arnau de Vilanova, Institut de Recerca Biomèdica de Lleida, Lleida, Spain; and.
authors.forename: Sònia
authors.initials: S
authors.lastname: Gatius
authors.affiliation: Oncologic Pathology Group, Departament de Ciències Mèdiques Bàsiques, Universitat de Lleida, Hospital Universitari Arnau de Vilanova, Institut de Recerca Biomèdica de Lleida, Lleida, Spain; and.
authors.forename: Felip
authors.initials: F
authors.lastname: Vilardell
authors.affiliation: Institute for Stem Cell Research, Medical Research Council Center for Regenerative Medicine, Edinburgh, United Kingdom.
authors.forename: Alexander
authors.initials: A
authors.lastname: Medvinsky
authors.affiliation: Oncologic Pathology Group, Departament de Ciències Mèdiques Bàsiques, Universitat de Lleida, Hospital Universitari Arnau de Vilanova, Institut de Recerca Biomèdica de Lleida, Lleida, Spain; and.
authors.forename: Xavier
authors.initials: X
authors.lastname: Matias-Guiu
authors.affiliation: Oncologic Pathology Group, Departament de Ciències Mèdiques Bàsiques, Universitat de Lleida, Hospital Universitari Arnau de Vilanova, Institut de Recerca Biomèdica de Lleida, Lleida, Spain; and.
authors.forename: Xavier
authors.initials: X
authors.lastname: Dolcet
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D017353:Gene Deletion; D006412:Hematopoietic Stem Cells / Q000166:cytology; D019426:Integrases / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D017493:Leukocyte Common Antigens / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009196:Myeloproliferative Disorders / Q000235:genetics* / Q000378:metabolism*; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000378:metabolism*
chemical_list: C045073:Cre recombinase; D019426:Integrases; D017493:Leukocyte Common Antigens; C516770:Ptprc protein, mouse; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse