The role of MYC in the transformation and aggressiveness of ‘indolent’ B-cell malignancies

Abstract

MYC was found to be involved in many germinal center derived lymphomas, and more recently in the histological transformation of indolent mature B-cell malignancies, such as follicular lymphoma (FL), chronic lymphocytic leukemia (CLL) and mucosa-associated lymphoid tissue lymphoma (MALT) to aggressive diffuse large B-cell lymphoma (DLBCL). Pathological MYC activity gain in lymphomas is able to overcome its regulation by repressors, which leads to bypassing the affinity-based selection of B-cells. Arguably the MYC activity gain is the most constantly observed phenomenon (>70% of cases) in transformed FL/MALT/CLL (Richter’s transformation) and co-occurs with specific aberrations such as the loss of p53, CDKN2A/B, or gain of BCL2/BCL6. Here we summarize recent progress in the understanding of MYC regulatory network in lymphoma B-cells and highlight its involvement in lymphomas’ histological transformation by regulating cyclins, CDKs, p21, p27, BCL2, E2F, FOXP1, BCR signaling components, and non-coding microRNA (miRNA) genes such as miR-150, miR-29, miR-17-92, and miR-34a.

Keywords:

• Lymphomas
• indolent mature B-cell malignancies
• transformation
• MYC
• microRNA

Author contributions

D.F. and M.M. wrote the manuscript.

Acknowledgments

Figures 1–3 were created using BioRender graphical tool.

Disclosure statement

The authors declare no competing financial interests.

Additional information

Funding

This study was financially supported by the Ministry of Health of the Czech Republic [grant No. NV18-03-00054]. All rights reserved.