Follicular lymphoma, a B cell malignancy addicted to epigenetic mutations

ABSTRACT

While follicular lymphoma (FL) is exquisitely responsive to immuno-chemotherapy, many patients follow a relapsing remitting clinical course driven in part by a common precursor cell (CPC) population. Advances in next generation sequencing have provided valuable insights into the genetic landscape of FL and its clonal evolution in response to therapy, implicating perturbations of epigenetic regulators as a hallmark of the disease. Recurrent mutations of histone modifiers KMT2D, CREBBP, EP300, EZH2, ARIDIA, and linker histones are likely early events arising in the CPC pool, rendering epigenetic based therapies conceptually attractive for treatment of indolent and transformed FL. This review provides a synopsis of the main epigenetic aberrations and the current efforts in development and testing of epigenetic therapies in this B cell malignancy.

KEYWORDS:

• Epigenetic mutations
• epigenetic therapies
• EZH2 inhibitors
• follicular lymphoma
• HDAC inhibitors

Disclosure of potential conflicts of interest

Jude Fitzgibbon has received research funding from Epizyme.

Funding

K Korfi, S Ali, J Heward and J Fitzgibbon are supported by Cancer Research UK Program Grant [C15966/A15968] and Bloodwise Program Grant [15002]. S Ali is also a recipient of Cancer Research UK Clinical Careers Committee research bursary [C56515/A21397].