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Review
. 2019 Sep 8;20(18):4417.
doi: 10.3390/ijms20184417.

Advances in Molecular Biology and Targeted Therapy of Mantle Cell Lymphoma

Pavel Klener  1   2
Affiliations
Review

Advances in Molecular Biology and Targeted Therapy of Mantle Cell Lymphoma

Pavel Klener. Int J Mol Sci. .

Abstract

Mantle cell lymphoma (MCL) is a heterogeneous malignancy with a broad spectrum of clinical behavior from indolent to highly aggressive cases. Despite the fact that MCL remains in most cases incurable by currently applied immunochemotherapy, our increasing knowledge on the biology of MCL in the last two decades has led to the design, testing, and approval of several innovative agents that dramatically changed the treatment landscape for MCL patients. Most importantly, the implementation of new drugs and novel treatment algorithms into clinical practice has successfully translated into improved outcomes of MCL patients not only in the clinical trials, but also in real life. This review focuses on recent advances in our understanding of the pathogenesis of MCL, and provides a brief survey of currently used treatment options with special focus on mode of action of selected innovative anti-lymphoma molecules. Finally, it outlines future perspectives of patient management with progressive shift from generally applied immunotherapy toward risk-stratified, patient-tailored protocols that would implement innovative agents and/or procedures with the ultimate goal to eradicate the lymphoma and cure the patient.

Keywords: B-cell receptor signaling; cell cycle; mantle cell lymphoma.

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Conflict of interest statement

The author declares no conflict of interest.

Figures

Figure 1
Figure 1
Pathogenesis of MCL. The Figure displays step-by-step accumulation of disease-critical mutations since early acquisition of t(11,14), ATM deletion, de novo expression of SOX11 (in nodal MCLs) to aggressive disease with TP53 aberration, complex molecular–cytogenetic alterations or even complex karyotype changes.
Figure 2
Figure 2
Cell cycle deregulation in MCL. MYC, MDM2, RB1, CCND1, CDKN2A.
Figure 3
Figure 3
BCR signaling in MCL (asterisks indicate recurrently mutated genes in MCL; PIP2 = Phosphatidylinositol (4,5)-bisphosphate; PIP3 = phosphatidylinositol (3,4,5)-trisphosphate; DAG = diacylglycerole; PDK1 = phosphoinositide-dependent kinase 1).
Figure 4
Figure 4
Current and future treatment algorithms in front-line and salvage therapy of MCL.
See this image and copyright information in PMC

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