Diverse B-cell specific transcriptional contexts of the BCL2 oncogene in mouse models impacts pre-malignant development
L. Zawil, T. Marchiol, B. Brauge, A. Saint-Amand, C. Carrion, E. Dessauge, C. Oblet, S. Le Noir, F. Mourcin, F. Jouan, P. Derouault, M. Alizadeh, M. Brousse, Y. El Makhour, C. Monvoisin, S. Leonard, S. Durand-Panteix, K. Tarte, M. Cogne
Abstract
Follicular lymphoma (FL) is the most common indolent form of non-Hodgkin lymphoma arising from malignant germinal center (GC) B-cells. The genetic hallmark that leads to the development of FL is the t(14:18) which occurs early in the bone marrow during B cell development, thereby placing the anti-apoptotic BCL2 gene under the direct control of the transcriptional enhancers in 3 of immunoglobulin heavy chain locus (IgH 3RR) and leading to the constitutive expression of the BCL2 protein. To assess the impact of the BCL2 deregulation on B-cell fate and try to reproduce FL development in mice, two models were designed: the Ig{kappa}-BCL2 (Knock in of the BCL2 in the light chain Ig kappa locus) and the 3RR-BCL2 (Transgene containing BCL2 and a micro-3RR), both containing the full BCL2 promoter region.
02 /Specification & Classification
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