A subpopulation of B-cells in Chronic Lymphocytic Leukemia (CLL) displaying high expression of activated induced cytidine deaminase (AID) and ongoing class switch recombination (CSR) is linked to poor prognosis

PALACIOS FLORENCIA; MORENO PILAR; MORANDE PABLO; ABREU CECILIA; CORREA AGUSTÍN; PORRO VALENTINA; LANDONI A; GABUS R; BIANCHI SERGIO; OPPEZZO PABLO

Viña del Mar, Chile

Congreso; 9th Latin American Congress of Immunology; 2009

AID is a key molecule required to induce immunoglobulin CSR and somatic hypermutation (SHM).Although, its expression occurs after stimulation of B-cells, AID is constitutively expressed in severallymphomas suggesting an association between its expression and lymphoproliferative disorders.According to the occurrence or not of SHM in VH genes, CLL can be classified in two groups: onedisplaying unmutated VDJ segments and poor prognosis; the other with mutated ones and goodoutcome. We previously reported that AID over-expression mainly occurs in unmutated CLL patientsand is associated to the presence of a subset of tumoral B-cells with ongoing CSR. Though thepresence of an active proliferative pool has been associated to poor outcome in CLL, the definition ofthis population remains elusive.The aim of this study was to determine whether the small subset of tumoral cells displaying activeCSR constitute this proliferative pool. Our results show that a high expression of AID is restricted totumoral cells ongoing CSR and that the presence of this subpopulation is associated to poor prognosis.Interestingly, the expression of molecular markers related to proliferation and disease progression (Ki-67, c-myc, BCL-2, CD49, and CCL3/CCL4 chemokines) is significantly higher in this pool comparedwith their counterpart of IgM leukemic cellsOverall, our work shows that the subset of tumoral B-cells with ongoing CSR accounts for almost allAID expression displays a high proliferative potential and, more importantly, is associated to diseaseprogression.