Abstract
Mantle cell lymphoma (MCL) is a malignant lymphoproliferative B-cell disorder that does not occur spontaneously in mice but experimental mice model have been developed. Recently two different mice models prone to develop MCL-like lymphomas were generated: c-myc-3'RR/Cdk4(R24C) mice and c-myc-3'RR/p53+/- mice. Comparison of their gene expression profiles does not highlight specific differences other than those in relation with their specific mutational status (i.e., Cdk4(R24C) mutation or p53 mutations). We propose that similarly to typical human MCL and its blastoid or cyclin-D1 variants that correspond to the same genetic entity, MCL-like lymphomas of c-myc-3'RR/ p53+/- mice and c-myc-3'RR/Cdk4(R24C) mice represent a spectrum of the same entity.
Highlights
Mantle cell lymphoma (MCL) is a malignant lymphoproliferative B-cell disorder derived from naïve pregerminal center CD5+ cells [1]
We explored the potential similar biological entity of these two mice models of MCL-like lymphomas by comparing their gene expression profiles
Animal works has been conducted according to French laws. c-myc-3’RR transgenic mice are prone to BL-like lymphomas [4]
Summary
Mantle cell lymphoma (MCL) is a malignant lymphoproliferative B-cell disorder derived from naïve pregerminal center CD5+ cells [1]. Cdk regulation by INK4 while c-myc is overexpressed in B-cells (in a c-myc-3’RR transgenic background prone to develop Burkitt lymphoma (BL)-like lymphomas [4]) leads to the development (in double mutant c-myc3’RR/Cdk4R24C mice) of lymphoid malignancies closely resembling human MCL [5]. It remains unclear what are the common molecular and genetic pathways explaining the convergence of these two mice models towards the same lymphoma phenotype In both situations, MCL-like lymphomas express similar membrane B-cell differentiation markers (B220+CD19+IgM+IgD+ CD5+CD23-) but arise with different kinetics (3 months vs 6 months for c-myc-3’RR/p53+/- mice and c-myc-3’RR/ Cdk4R24C mice, respectively), with a different proteomic signature (Cdk6/cyclin D complexes vs Cdk4/cyclin D complexes for c-myc-3’RR/p53+/- mice and c-myc3’RR/Cdk4R24C mice, respectively), and in relation with a different mutational status We explored the potential similar biological entity of these two mice models of MCL-like lymphomas by comparing their gene expression profiles
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