Title: The Role of Major Histocompatibility Complex Polymorphisms in the Incidence and Outcome of Non-Hodgkin Lymphoma
Volume: 5
Issue: 4
Author(s): Jacek Nowak, Przemyslaw Juszczynski and Krzysztof Warzocha
Affiliation:
Keywords:
Genetic polymorphism, major histocompatibility complex, Non-Hodgkin lymphoma, pathogenesis
Abstract: Major histocompatibility complex (MHC) genes are involved in various mechanisms of pathogenesis and immunoediting of non-Hodgkin ’ s lymphoma (NHL). MHC class III polymorphisms, located within tumor necrosis factor (TNF) family gene cluster, have diverse expression in normal individuals and lymphoma patients, and their expression depends on the allelic version. Certain HLA class I and II gene products are involved in the tumor peptide presentation and ligation of specific T-cell receptors (TCR). They are involved in NHL pathogenesis either directly or as a consequence of the linkage disequilibrium (LD) with causative genes. TNF polymorphic alleles and closely located nuclear factor of kappa light polypeptide gene enhancer in B-cell inhibitor like 1 (NFKBIL1) may lead to up-regulation of nuclear factor kappa B (NFκB) and adverse outcome of certain subsets of diffuse large B-cell lymphomas. In addition, HLA class I ligation to the natural killer (NK)-cell immunoglobulin-like receptors (KIR) plays a critical role in immunosurveillance of the tumors, which may result in deterioration of NHL outcome, especially when the repertoire of MHC-KIR interaction is reduced. This review summarizes clinical data of MHC allele and haplotype polymorphisms and their pleiotropic or epistatic links to the pathogenesis of NHL.
