Identification of B94 (TNFAIP2) as a potential retinoic acid target gene acute promyelocytic leukemia

Michael E. Rusiniak, Min Yu, Douglas T. Ross, Erin C. Tolhurst, James L. Slack

Research output: Contribution to journalArticle

57 Scopus citations

Abstract

Acute promyelocytic leukemia (APL) is characterized by a block to myeloid differentiation caused by expression of the fusion oncoprotein promyelocytic leukemia-retinoic acid receptor α (PML-RARα). The purpose of this study was to identify genes that are regulated in a PML-RARα-dependent fashion by retinoic acid (RA), 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-RARα (TF1-PR cells). The B94 gene (TNFAIP2; Unigene Hs.101382), originally identified as a tumor necrosis factor α- inducible gene in endothelial cells, was one of several genes found to be induced by RA specifically in TF1-PR cells, but not in TF1-neo (control) cells. The induction of B94 was most pronounced in cells expressing the PML- RARα short isoform and was negligible in cells that expressed a mutant PML- RARα 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-RARα 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 M0-M2, 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-RARα in APL.

Original languageEnglish (US)
Pages (from-to)1824-1829
Number of pages6
JournalCancer research
Volume60
Issue number7
StatePublished - Apr 1 2000

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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