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Follicular Lymphoma: Epidemiology, Pathogenesis and Initiating Events

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Follicular Lymphoma

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Abstract

Follicular lymphoma (FL) is the most common indolent lymphoma in the United States and Western Europe and arises from a complex interplay of genetic and environmental factors, though most patients do not have clearly identifiable risk factors at presentation. A family history of non-Hodgkin lymphoma (NHL), single-nucleotide polymorphisms (SNPs) in both HLA and non-HLA regions, exposure to pesticides and chemical solvents, Sjogren’s syndrome, heavy smoking (especially in women), obesity and sedentary lifestyle have been associated with increased risk. Follicular lymphoma (FL) cells have dependence on a microenvironment mimicking the normal lymph node germinal centre (GC). The characteristic t(14;18) BCL2-IGH translocation, present in around 85% of FL cases, is recognised as the likely initial necessary although not sufficient abnormality present early in a multihit pathway which culminates in clinically overt follicular lymphoma. The role of the microenvironment in FL appears to simultaneously support growth and survival of the neoplastic cells and suppress the antitumour immune response. There is progression from early genetic hits to a dynamic evolution of subclones, in which subsequent genetic hits may be variably seen in clinically evident clonal expansions, in situ disease or sequestration within niches such as the bone marrow, with subclones re-emerging following therapy or resulting in transformation to high-grade lymphoma. Better understanding of issues such as the drivers of germinal centre re-entry of early FL clones, the nature of the impaired B-cell receptor (BCR) signalling and the complex tumour microenvironment may present targets for innovative therapeutic strategies.

All others contributed equally to this work

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    Authors and Affiliations

    1. Department of Haematology, Sir Charles Gairdner Hospital, Nedlands, WA, Australia

      Zi Yun Ng & Chan Yoon Cheah

    2. Department of Anatomical Pathology, Pathwest QEII Medical Centre, Nedlands, WA, Australia

      Connull Leslie

    3. School of Biomedical Sciences, University of Western Australia, Crawley, WA, Australia

      Connull Leslie

    4. Medical School, University of Western Australia, Crawley, WA, Australia

      Chan Yoon Cheah

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    1. Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

      Nathan H. Fowler

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    Ng, Z.Y., Leslie, C., Cheah, C.Y. (2020). Follicular Lymphoma: Epidemiology, Pathogenesis and Initiating Events. In: Fowler, N. (eds) Follicular Lymphoma. Springer, Cham. https://doi.org/10.1007/978-3-030-26211-2_1

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