Submitted by Claudia Pommerenke (Leibniz Institute DSMZ, Germany) on Jan 22 2019
Platform: microarray – [HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array
Pubmed: 31141539
Summary NKL homeobox genes encode developmental transcription factors regulating basic processes in cell differentiation. According to their physiological expression pattern in early hematopoiesis and B-cell development, particular members of this homeobox gene subclass constitute an NKL-code. These B-cell specific genes generate a regulatory network and their deregulation is implicated in B-cell lymphomagenesis. Epstein-Barr virus (EBV) infects B-cells and influences the activity of signalling pathways including JAK/STAT and several genes encoding developmental regulators. Therefore, EBV-infection impacts the pathogenesis and the outcome of B-cell malignancies including Hodgkin lymphoma and diffuse large B-cell lymphoma (DLBCL). Here, we isolated EBV-positive and EBV-negative subclones from the DLBCL derived cell line DOHH-2. These subclones served as model to investigate the role of EBV in deregulation of the B-cell specific NKL-code members HHEX, HLX, MSX1 and NKX6-3. We showed that the EBV-encoded factors LMP1 and LMP2A activated the expression of HLX via STAT3. HLX in turn repressed NKX6-3, SPIB and IL4R which normally mediate plasma cell differentiation. In addition, HLX repressed pro-apoptotic factor BCL2L11/BIM supporting cell survival. Thus, EBV aberrantly activated HLX thereby disturbing both B-cell differentiation and apoptosis in DLBCL. The results of our study contribute to better understand the pathogenic role of EBV in B-cell malignancies.
ID | Title | Cell Type | Timepoint | Reported Virus | Virus Species | Exclusion Reason |
---|---|---|---|---|---|---|
GSM3573691 | DOHH-2_control | diffuse large B-cell lymphoma cell ![]() |
none | Uninfected | ||
GSM3573692 | DOHH-2_EBV | diffuse large B-cell lymphoma cell ![]() |
unknown | EBV | Human gammaherpesvirus 4 |