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Leuk Lymphoma. 2020 Mar;61(3):510-524. doi: 10.1080/10428194.2019.1675877. Epub 2019 Oct 20.

The role of MYC in the transformation and aggressiveness of 'indolent' B-cell malignancies.

Filip D1,2, Mraz M1,2.

Author information

1
Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
2
Department of Internal Medicine, Haematology and Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic.

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; MYC; indolent mature B-cell malignancies; microRNA; transformation

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