RESUMO
Activation of cytokine signaling via the leukemia inhibitory factor receptor (LIFR) plays an integral role in hematopoiesis, osteogenesis, and placental development, along with mediating neurotrophic mechanisms. However, the regulatory control of the LIFR gene has remained largely unexplored. Here, we characterize the LIFR gene as a novel target of the RUNX1 transcription factor. The RUNX1 transcription factor is an essential regulator of hematopoiesis and is a frequent target of point mutations and chromosomal alterations in leukemia. RUNX1 regulates hematopoiesis through its control of genes important for hematopoietic cell growth, proliferation, and differentiation, including a number of cytokines and cytokine receptors. LIFR is regulated by two alternate promoters: a placental-specific and a ubiquitously active general promoter. We show that both of these promoters are regulated by RUNX1. However, in myeloid cells LIFR expression is driven solely by the general LIFR promoter with our data indicating that the placental promoter is epigenetically silenced in these cells. While RUNX1 activates the LIFR general promoter, the oncogenic RUNX1-ETO fusion protein generated by the t(8;21) translocation commonly associated with acute myeloid leukemia represses promoter activity. The data presented here establish LIFR as a transcriptional target of RUNX1 and suggest that disruption of RUNX1 activity in myeloid cells may result in altered LIFR signaling in these cells.
Assuntos
Subunidade alfa 2 de Fator de Ligação ao Core/metabolismo , Receptores de OSM-LIF/metabolismo , Western Blotting , Diferenciação Celular/genética , Diferenciação Celular/fisiologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Proliferação de Células/fisiologia , Imunoprecipitação da Cromatina , Aberrações Cromossômicas , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Humanos , Células Mieloides/metabolismo , Mutação Puntual/genética , Regiões Promotoras Genéticas/genética , Ligação Proteica/genética , Ligação Proteica/fisiologia , Receptores de Citocinas/genética , Receptores de Citocinas/metabolismo , Receptores de OSM-LIF/genéticaRESUMO
Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections were assessed among 81 Bahraini and 34 Saudi hemodialysis patients and 7714 Bahraini and 2330 Saudi blood donors. Higher prevalence of HCV (9.24% vs 0.30%), hepatitis B surface antigen (5.88% vs 0.62%) were seen in patients versus control patients, and in Saudi patients compared with Bahraini patients. HCV genotypes were HCV 1a/1b plus HCV 4 among Bahraini patients and HCV 2/2a plus HCV 4 among Saudi patients. This is the first report on viral hepatitis in Bahrain and the first to compare HBV/HCV among dialysis patients in the Eastern Arabian Peninsula.