A NOVEL INTERFERON-INDUCIBLE GENE EXPRESSED DURING MYELOID DIFFERENTIATION

The acute promyelocytic leukemia cell line, NB4, can be induced to dif ferentiate to mature granulocytes by retinoic acid treatment. A novel retinoic acid-inducible cDNA clone, designated RI58, was isolated from a cDNA library constructed from retinoic acid-treated NB4 cells by di fferential hybridization. RI58 cDNA encodes a protein of 58kDa which h as a similarity in its amino acids sequence to interferon (IFN)inducib le proteins, In addition, RI58 was induced by recombinant human IFN-al pha (rhIFN-alpha) in NB4 cells, RI58 was detectable within 4 hours pos t-stimulation with rhIFN-alpha, while it took as long as 1 day after l etinoic acid stimulation, Culture supernatant from retinoic acid-treat ed NB4 cells also induced RI58 expression similarly as rhIFN-alpha, Th is activity in culture supernatant was inhibited by anti-leukocyte IFN antiserum which showed specific reactivity to rhIFN-alpha. These resu lts indicate that RI58 is induced by retinoic acid stimulation through autocrinally secreted IFN-alpha from NB4 cells. In the retinoic acid- treated NB4 cells, the expression of RI58 was increased along the proc ess of differentiation. On the other hand, it was expressed constituti vely in untreated non-hematopoietic cell lines and mature hematopoieti c cell lines.