Project description:Hodgkin lymphoma is derived from germinal center / post-germinal center B cells. Gene expression profilies of micodissected Hodkin Reed Sternberg cells (n=29) were compared to microdissected germinal centers (n=5)
Project description:Hodgkin lymphoma is derived from germinal center / post-germinal center B cells. Gene expression profilies of micodissected Hodkin Reed Sternberg cells (n=29) were dichotomized into primary treatment failure (n=14) and primary treatment succeses (n=15). Treament failure was defined as refractory disease or progression at any time after ABVD chemotherapy.
Project description:Hodgkin lymphoma is derived from germinal center / post-germinal center B cells. Gene expression profilies of the Hodgkin lymphoma cell lines were compared to 5 samples of CD77+ centroblasts derived from reactive tonsils
Project description:Hodgkin lymphoma is derived from germinal center / post-germinal center B cells. To determine differentially expressed genes between Hodgkin Reed Sternberg cells and their presumed cell of origin we investigated the expression profiles of 5 commonly used Hodgkin lymphoma cell lines as compared to reactive germinal centers.
Project description:The pathogenesis of nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) and its relationship to other lymphomas are largely unknown. This is partly due to the technical challenge of analyzing its rare neoplastic L&H cells, which are dispersed in an abundant non-neoplastic cellular microenvironment. We performed a genome-wide expression study of microdissected lymphocytic and histiocytic (L&H) lymphoma cells in comparison to normal and other malignant B cells, which indicates a relationship of L&H cells to and/or origin from germinal center B cells at transition to memory B cells. L&H cells show a surprisingly high similarity to the tumor cells of T cell-rich B cell lymphoma and classical Hodgkin lymphoma, a partial loss of their B cell phenotype and deregulation of many apoptosis-regulators and putative oncogenes. Importantly, L&H cells are characterized by constitutive NF-κB activity and aberrant ERK signaling. Thus, these findings shed new light on the nature of L&H cells, revealed several novel pathogenetic mechanisms in NLPHL, and may help in differential diagnosis and lead to novel therapeutic strategies. Experiment Overall Design: Analysis of differential gene expression in primary human lymphoma cells of nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) in comparison with primary lymphoma cells of classical Hodgkin lymphoma cells and other B-non-Hodgkin lymphoma (B-NHL) samples and subsets of non-neoplastic B lymphocytes isolated from blood or tonsils. 67 gene expression profiles were analysed.
Project description:Burkitt lymphoma (BL) is a highly aggressive B cell non-Hodgkin lymphoma (B-NHL), which originates from germinal center (GC) B cells and harbors translocations deregulating the MYC oncogene. A comparative analysis of microRNAs (miRNAs) expressed in normal and malignant GC B cells identified miR-28 as significantly down-regulated in BL, as well as in other GC-derived B-NHL. We show that re-expression of miR-28 impairs cell growth and clonogenic properties of BL cells by modulating several targets including MAD2L1, a component of the spindle checkpoint whose down-regulation is essential in mediating miR-28-induced growth-arrest, and BAG1, an activator of the ERK pathway.
Project description:Polatuzumab Vedotin (Pola-V) is an antibody-drug conjugate directed to the CD79B subunit of the B cell receptor (BCR). When combined with conventional immunochemotherapy, Pola-V improves outcomes in DLBCL. To identify molecular determinants of sensitivity to Pola-V, we used CRISPR-Cas9 screening for genes that modulated the toxicity of Pola-V for lymphomas or the surface expression of its target, CD79B. Our results reveal a striking impact of CD79B glycosylation on Pola-V epitope availability on the lymphoma cell surface and on Pola-V toxicity. Genetic, pharmacological, and enzymatic approaches that remove terminal sialic acid residues from N-linked glycans enhanced lymphoma killing by Pola-V. Pola-V toxicity was also modulated by KLHL6, a ubiquitin ligase that targets CD79B for degradation in normal and malignant germinal center B cells, explaining its recurrent inactivation in germinal center-derived lymphomas. Our findings suggest precision medicine strategies to optimize Pola-V as a lymphoma therapeutic.