title: Utility of LRF/Pokemon and NOTCH1 protein expression in the distinction between nodular lymphocyte-predominant Hodgkin lymphoma and classical Hodgkin lymphoma.
abstract: Classical Hodgkin lymphoma (CHL) and nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) are considered separate entities with different prognosis and treatment. However, morphologic features can be similar and immunohistochemical studies are essential in the distinction; thus, determination of additional biomarkers is of utmost importance. LRF/Pokemon is a proto-oncogene, an interacting partner co-expressed with BCL6 in germinal centers and highly expressed in diffuse large B-cell lymphoma and follicular lymphoma. Conversely, loss of the LRF gene in mouse hematopoietic stem cells results in complete block of early B cell development with concomitant Notch de-repression, indicating its critical role in B versus T cell fate decision at the hematopoietic stem cell stage. For the first time, we show that LRF/Pokemon is predominantly expressed in NLPHL cases as is BCL6 with low to absent NOTCH1 protein expression; while Hodgkin Reed-Sternberg (HRS) cells in CHL show low to absent BCL6 and LRF/Pokemon expression with higher NOTCH1 expression. We illustrate a potential functional interaction between LRF and BCL6 in NLPHL pathogenesis, and differential expression of LRF/Pokemon and NOTCH1 proteins in CHL thus showing differential expression, making for an additional diagnostic marker and therapeutic target.
authors: 1Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors: Olga
authors: O
authors: Bohn
authors: Takahiro
authors: T
authors: Maeda
authors: Alexander
authors: A
authors: Filatov
authors: Andrea
authors: A
authors: Lunardi
authors: Pier Paolo
authors: PP
authors: Pandolfi
authors: Julie
authors: J
authors: Teruya-Feldstein
mesh_terms: D000293:Adolescent; D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D006689:Hodgkin Disease / Q000175:diagnosis* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D000090063:Proto-Oncogene Mas; D051881:Receptor, Notch1 / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C000715470:MAS1 protein, human; C497761:NOTCH1 protein, human; D000090063:Proto-Oncogene Mas; D051881:Receptor, Notch1; D014157:Transcription Factors; C485514:ZBTB7A protein, human
keywords: Hodgkin lymphoma; LRF; Pokemon; classical Hodgkin lymphoma (cHL); nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL)