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The NKL-code for innate lymphoid cells reveals deregulated expression of NKL homeobox genes HHEX and HLX in ALCL

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE146391 | GEO | 2020/09/10

REPOSITORIES: GEO

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The NKL-code for innate lymphoid cells reveals deregulated expression of NKL homeobox genes HHEX and HLX in anaplastic large cell lymphoma (ALCL).

Project description: Not available

| S-EPMC7456612 | biostudies-literature

The NKL-code for innate lymphoid cells reveals deregulated expression of NKL homeobox genes HHEX and HLX in ALCL [II]

Project description: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.

2020-09-10 | GSE146390 | GEO

The NKL-code for innate lymphoid cells reveals deregulated expression of NKL homeobox genes HHEX and HLX in ALCL [I]

2020-09-10 | GSE146389 | GEO