Anti-TNFAIP2 monoclonal antibody, clone 8I2

TNF-induced protein 2 (TNFAIP2) is a primary response gene of TNF alpha. TNFAIP2 is highly expressed in immune cells and the urinary bladder. The expression of TNFAIP2 is regulated by multiple transcription factors and signalling pathways, including NF-kappa B, KLF5 and retinoic acid. Physiologically, TNFAIP2 appears to be a multiple functional mediator not only for inflammation, angiogenesis and tunneling nanotube (TNT) formation but also as a regulator of cell proliferation and migration. The expression of TNFAIP2 is frequently abnormal in human cancers and in infectious diseases. Due to its significant functions in cell proliferation, angiogenesis, migration and invasion, TNFAIP2 could be a potential diagnostic biomarker and therapeutic target for cancer.

Acute promyelocytic leukemia (APL) is characterized by a block to myeloid differentiation caused by expression of the fusion oncoprotein promyelocytic leukemia-retinoic acid receptor a (PML-RAR alpha), The purpose of this study was to identify genes that are regulated in a PML-RAR alpha-dependent fashion by retinoic acid (R4), because such genes may be integrally involved in APL pathogenesis and/or myeloid differentiation. A cDNA microarray approach was used to identify genes induced in response to RA in TF1 myeloid leukemia cells expressing PML-RAR alpha (TFI-PR cells), The B94 gene (TNFAIP2; Unigene Hs.101382), originally identified as a tumor necrosis factor cy-inducible gene in endothelial tells. was one of several genes found to be induced by RA specifically in TFI-PR cells, but not in TF1-neo (control) cells. The induction of B94 was most pronounced in cells expressing the PML-RAR alpha short isoform and was negligible in cells that expressed a mutant PML-RAR alpha protein containing a deletion of the PML coiled-coil domain, B94 induction by RA occurred within 1 h, did not require new protein synthesis, and was inhibited by actinomycin D, suggesting rapid transcriptional activation. B94 was also induced by RA in NB4, UF1, and HL-60 cells, but not in other hematopoietic cell lines tested, suggesting that its up-regulation by RA may be specific to cells that express PML-RAR alpha or are at the late myeloblast or promyelocyte stage of myeloid development. A screen of bone marrow cells from normal donors or patients with acute myelogenous leukemia showed that B94 was highly expressed in normal marrow and in marrow from patients with acute myelogenous leukemia French-American-British subtypes M-0-M-2, but was repressed in marrow cells from APL patients. Treatment of APL blasts in vitro with all-trans-RA resulted in up-regulation of B94 mRNA, These results suggest that B94 plays a role in myeloid development and support the hypothesis that B94 is a target gene of PML-RAR alpha in APL.