Molecular Pathogenesis of Mantle Cell Lymphoma

Abstract

Mantle cell lymphoma (MCL) is a mature B-cell neoplasm with heterogeneous clinical behavior molecularly characterized by the constitutive overexpression of cyclin D1 and deregulation of different signaling pathways. SOX11 expression determines an aggressive phenotype associated with accumulation of many chromosomal alterations and somatic gene mutations. A subset of patients with the SOX11-negative leukemic non-nodal MCL subtype follows an initial indolent clinical evolution and may not require treatment at diagnosis, although eventually may progress to an aggressive disease. We discuss the genetic and molecular alterations with impact on the cancer hallmarks that characterize the lymphomagenesis of the 2 MCL subtypes.

Keywords: CCND1; Cancer hallmarks; Gene mutations; Genome instability; Mantle cell lymphoma; Molecular pathogenesis; SOX11.

Figure 1.. MCL molecular subtypes.

The naïve B-cell with cyclin deregulation may evolve into two distinct molecular subtypes with different molecular and clinicopahtological characteristics.

Figure 2.. MCL hallmarks.

The conceptual framework encompasses many different cellular functions that transform normal cells into malignant cancer cells. All the related pathways involved in MCL pathogenesis may be globally grouped into five main hallmarks.