Diverse B-cell specific transcriptional contexts of the BCL2 oncogene in mouse models impacts pre-malignant development

Zawil, L.; Marchiol, T.; Brauge, B.; Saint-Amand, A.; Carrion, C.; Dessauge, E.; Oblet, C.; Le Noir, S.; Mourcin, F.; Jouan, F.; Derouault, P.; Alizadeh, M.; Brousse, M.; El Makhour, Y.; Monvoisin, C.; Leonard, S.; Durand-Panteix, S.; Tarte, K.; Cogne, M.

doi:10.1101/2021.10.28.466164

bioRxiv · 10.1101/2021.10.28.466164

Diverse B-cell specific transcriptional contexts of the BCL2 oncogene in mouse models impacts pre-malignant development

Zawil, L.·Marchiol, T.·Brauge, B.·Saint-Amand, A.·Carrion, C.·Dessauge, E.·Oblet, C.·Le Noir, S.·Mourcin, F.·Jouan, F.·Derouault, P.·Alizadeh, M.·Brousse, M.·El Makhour, Y.·Monvoisin, C.·Leonard, S.·Durand-Panteix, S.·Tarte, K.·Cogne, M.

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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.

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Zawil, L., Marchiol, T., Brauge, B., Saint-Amand, A., Carrion, C., Dessauge, E., Oblet, C., Le Noir, S., Mourcin, F., Jouan, F., Derouault, P., Alizadeh, M., Brousse, M., El Makhour, Y., Monvoisin, C., Leonard, S., Durand-Panteix, S., Tarte, K., Cogne, M.. 2021-10-28. Diverse B-cell specific transcriptional contexts of the BCL2 oncogene in mouse models impacts pre-malignant development. https://doi.org/10.1101/2021.10.28.466164

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