Expression data from adult mouse spleen

AIMP2-DX2 is known as a cancer-associated splicing variant of tumor suppressor, AIMP2, lacking exon 2 (shortly DX2 herein). However, it is not known whether its expression alone can drive tumorigenesis. Here we show that DX2 can induce the expansion of germinal center (GC) origin B lymphocytes and their infiltration into multi-organs in mouse model. In doxycycline-dependent inducible transgenic mice, monoclonal expansion of B cells with malignant transformation was developed in two out of seven cases. Induction of DX2 destabilized p53 and dysregulated cell cycle genes, leading to lymphomagenesis. Turning off DX2 induced the death of cancer cells, suggesting the significance of DX2 in the cancer cell growth. Consistently with the mouse phenotypes, higher expression of DX2 was observed in human Burkitt lymphoma and GCB diffuse large B cell lymphoma (DLBCL). Expression of DX2 was confirmed in a subset of GC origin lymphoma obtained from separate cohort using RNA silver in situ hybridization (SISH). In differentially expressed gene analysis, the high DX2 subset was well segregated in GCB lymphomas. High expression of transcription factor MEF2B and its target genes were observed in DX2-associated GCB DLBCL both at RNA and protein level, implying the pathological connection of DX2 with MEF2B in human lymphomagenesis. Functional significance of DX2 for cell viability was confirmed in human DLBCL cell line. In summary, our data suggest DX2 as a driver of lymphomagenesis and potential therapeutic target especially for GCB lymphomas

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