DEVELOPMENT OF A NOVEL MURINE MODEL FOR THE STUDY OF CHRONIC LYMPHOCYTIC LEUKEMIA OVEREXPRESSING THE MUTAGENIC ENZYME AID

MORANDE PABLO; PRIETO DANIEL; ABREU CECILIA; SOTELO NATALIA; CORREA AGUSTÍN; ORTEGA CLAUDIA; CRISPO MARTINA; OPPEZZO PABLO

Mar del Plata

Congreso; LIX REUNIÓN CIENTÍFICA ANUAL Sociedad Argentina de Investigación Clínica LXII REUNIÓN ANUAL Sociedad Argentina de Inmunología; 2014

Cronic lymphocytic leukemia (CLL) is a hematologic diseasecharacterized by slow accumulation of clonal CD5+ B lymphocytesin peripheral blood (PB), bone marrow and lymphoid organs.Activation-induced cytidine deamiase (AID) is an enzyme able toinduce DNA mutations and whose activity is tightly regulated. UncontrolledAID activity is related to the origin of several neoplasmdiseases. We previously described that progressive CLL patientsaberrantly express AID in CLL B-cells of PB (Oppezzo et al, Blo od2005), specifically in a small proliferative subset (Palacios et al.,Blood 2010 and Leukemia 2014). The aim of the present work was294 MEDICINA - Volumen 74 - (Supl. III), 2014to evaluate the role of AID in CLL disease progression, planning isto determine weather during the development of the leukemia AIDcan introduce DNA changes that lead to a more aggressive tumordevelopment. To that aim we used a murine model that mimics aprogressive CLL disease, the transgenic Eu-TCL1 mice. This straindevelops an aggressive IgM+CD5+ leukemia starting at 8 monthsof age and due to over expression of the TCL1 gene in B cells.We crossed TCL1 mice with AID transgenic mice and obtainedthe double transgenic AID/TCL1 mice (DT), which resulted viableand showed no evident inborn alterations. Gene presence at theDNA genomic level was verified by PCR and quantitative PCR(qPCR); and gene expression was measured by qPCR in PB andspleen cells, for both TCL1 and AID transgenes. DT mice expressedTCL1 and showed higher expression of AID as compared toits monotransgenic TCL1 control, for both SP and spleen cells(n=5, p