Human A1, a Bcl-2-related gene, is induced in leukemic cells by cytokines as well as differentiating factors

Abstract

Based on previously published observations regarding the prohomologous to the newly described human A1, 14 or 15 tective effects of interleukin-1 (IL-1) and tumor necrosis factor a Bcl-2-related gene. alpha (TNF␣) against gamma radiation, alkylating agents andIn this study, we have investigated the effects of IL-1/TNF␣ ultraviolet radiation, we hypothesized that the protection as well as several differentiating factors on the expression of against such DNA damaging treatments can be the result of a the new gene in different leukemic cell lines.'stress'-like response induced by these cytokines and mediated by early response cellular gene(s). By applying the mRNA differential display to RNA obtained from A549 lung carcinoma cell line that was incubated with 50 ng/ml IL-1 for 0, 1, 2, and 6 h, we identified several cDNA fragments that correspond to Materials and methodsgenes regulated by IL-1. The full length cDNA for one fragment was obtained using 5ЈRACE, cloned, sequenced, and found to Reagents be homologous to human A1, a Bcl-2-related gene. In this study, we report that the expression of human A1 is either absent or present at low levels in leukemic cells, while it is All-trans retinoic acid (ATRA), phorbol 12-myristate 13-ace- Lake City, UT, USA) and used at 1.2% to induce differen-

Nuclear Factor κB-Dependent Activation of the Antiapoptoticbfl-1Gene by the Epstein-Barr Virus Latent Membrane Protein 1 and Activated CD40 Receptor

“…In this regard, Bfl-1 might be viewed as a key determinant of cell fate for immature peripheral B cells. The strong induction of bfl-1 transcripts by proinflammatory cytokines in endothelial, leukemic, and hemopoietic cells is consistent with a role for protecting them from apoptotic extinction (17,67,68,84,93). Consistent with a role for NF-B in this process is the reduction in constitutive bfl-1 mRNA levels in B cell lines derived from c-Rel Ϫ/Ϫ mice (49).…”

“…Treatment of a variety of cell lines with the chemical agent phorbol-12-myristate 13-acetate (PMA), a well-known activator of NF-B, has been shown to upregulate bfl-1 mRNA levels in BL cell lines (93). We therefore investigated whether PMA, when used at the same concentration (10 Ϫ7 M) as that reported previously, could also activate the bfl-1 promoter.…”

NF-κB-Dependent Assembly of an Enhanceosome-Like Complex on the Promoter Region of Apoptosis Inhibitor Bfl-1/A1

“…Architectural factor HMGI-C was implicated in enhancing NF-B-mediated transcription and is rearranged in mesodermally derived tumors, such as B-and T-cell leukemias (4,37). The strong induction of bfl-1 transcripts by proinflammatory cytokines in endothelial, leukemic, and hemopoietic cells is consistent with a role in protecting them from apoptotic extinction (14,27,34,42). The observation that Bfl-1/A1 gene expression is also sharply induced in mature B cells that have entered the longlived pool highlights its possible contribution to cell survival during negative selection (60).…”

“…bfl-1 gene expression is generally confined to immune cells and tissues, in a pattern similar to that of NF-B itself, and is strongly induced by cytokine stimulation of leukemic, endothelial, and hemopoietic cells (27,34,42,60). Constitutively elevated levels of bfl-1 transcripts are seen in mature neutrophils and are selectively induced in long-lived peripheral B cells (60).…”

Upregulation of bfl-1 is a potential mechanism of chemoresistance in B-cell chronic lymphocytic leukaemia

“…In humans, bfl-1 expression is found in various types of haematopoietic cells in the bone marrow, in germinal centres of peripheral lymphoid organs, haematopoietic cells of fetal liver (Jung-Ha et al, 1998), endothelial cells and in smooth muscle cells (Karsan et al, 1996). bfl-1 is a direct transcriptional target of NF-kB (Zong et al, 1999), and is inducible by inflammatory stimuli in various cell types (Karsan et al, 1996;Moreb and Schweder et al, 1997). In B lymphocyte-derived cell lines and in primary B cells bfl-1 is induced by CD40 ligation and has been shown to protect from apoptosis triggered by ligation of the Bcell receptor or Fas (Kuss et al, 1999;Craxton et al, 2000).…”