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Molecular pathogenesis of mantle cell lymphoma
Pedro Jares, … , Dolors Colomer, Elias Campo
Pedro Jares, … , Dolors Colomer, Elias Campo
Published October 1, 2012
Citation Information: J Clin Invest. 2012;122(10):3416-3423. https://doi.org/10.1172/JCI61272.
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Review Series Article has an altmetric score of 11

Molecular pathogenesis of mantle cell lymphoma

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Abstract

Mantle cell lymphoma is a B cell malignancy in which constitutive dysregulation of cyclin D1 and the cell cycle, disruption of DNA damage response pathways, and activation of cell survival mechanisms contribute to oncogenesis. A small number of tumors lack cyclin D1 overexpression, suggesting that its dysregulation is always not required for tumor initiation. Some cases have hypermutated IGHV and stable karyotypes, a predominant nonnodal disease, and an indolent clinical evolution, which suggests that they may correspond to distinct subtypes of the disease. In this review, we discuss the molecular pathways that contribute to pathogenesis, and how improved understanding of these molecular mechanisms offers new perspectives for the treatment of patients.

Authors

Pedro Jares, Dolors Colomer, Elias Campo

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Figure 1

Hypothetical models of two different molecular subtypes of MCL.

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Hypothetical models of two different molecular subtypes of MCL.
The naiv...
The naive B cell carrying the t(11;14) colonizes the mantle zone of the lymphoid follicle and generates an in situ MCL lesion. Most MCLs evolve from these cells or cells in the marginal zone with no or limited IGHV somatic mutations. These tumors express SOX11, are genetically unstable, and tend to accumulate alterations in genes dysregulating cell cycle, DNA damage response pathways, and cell survival mechanisms. Alternatively, some cells with the t(11;14) may enter the germinal center and undergo IGHV somatic hypermutations. These cells are genetically stable and do not express SOX11. The tumors derived from these cells tend to spread to the peripheral blood and spleen more than to lymph nodes. The disease seems to be stable for long periods of time, but some of these tumors may acquire mutations in genes such as TP53 that lead to disease progression. Intriguingly, some tumors with the pathological and genetic features of MCL do not carry translocations of the CCND1, CCND2, and CCND3.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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