Genomics of Nodular Lymphocyte-Predominant Hodgkin Lymphoma (NLPHL)

LP cells express B-cell antigens (e.g., CD19, CD20, CD22, and CD79A) and B-cell transcription factors (e.g., OCT2 and BOB1).[21,22]

The expression of Bcl-6 and the presence of somatic hypervariants in the variable region of rearranged Ig heavy chain genes point to a germinal center derivation for LP cells.[23,24]

IgD expression connotes a distinct type of NLPHL that is associated with a very high male-to-female ratio (>10:1).[25,26] An evaluation of the antigenic specificity of the B-cell receptor in cases of IgD-positive NLPHL found that in 7 of 8 cases (6 of 8 patients aged ≤18 years), the B-cell receptor recognized the DNA-directed RNA polymerase (RpoC) from Moraxella catarrhalis.[27] High-titer, light-chain-restricted anti-RpoC IgG1 serum-antibodies were observed in these patients. In addition, MID/hag is a superantigen expressed by M. catarrhalis that binds to the Fc domain of IgD and activates IgD-positive B cells. These observations support a role for M. catarrhalis in the development and maintenance of IgD-positive NLPHL.

Genomic analysis of NLPHL is limited to a small number of patients using gene panels to evaluate microdissected specimens containing LP cells. Genes with recurring variants include SOCS1 (an inhibitor of JAK-STAT pathway signaling), DUSP2 (a dual specificity phosphatase that is a negative regulator of the MAP kinase pathway), JUNB (a transcription factor in the activator protein-1 family), and SGK1 (a serine-threonine kinase).[28-30]