RESUMEN
The coincident downregulation of NR4A1 and NR4A3 has been implicated in myeloid leukemogenesis, but it remains unknown how these two genes function in myeloid cells and how their combined downregulation promotes myeloid leukemogenesis. Since NR4A1 abrogation is thought to confer a survival and proliferation advantage to myeloid cells, we hypothesized that downregulation of NR4A3 may have a complementary effect on myeloid cell differentiation. First, we tested the association between differentiation status of leukemic cells and NR4A3 expression using two large clinical datasets from patients with different acute myeloid leukemia (AML) subtypes. The analysis revealed a close association between differentiation status and different subtypes of AML Then, we probed the effects of differentiation-inducing treatments on NR4A3 expression and NR4A3 knockdown on cell differentiation using two myeloid leukemia cell lines. Differentiation-inducing treatments caused upregulation of NR4A3, while NR4A3 knockdown prevented differentiation in both cell lines. The cell culture findings were validated using samples from chronic myeloid leukemia (CML) patients at chronic, accelerated and blastic phases, and in acute promyelocytic leukemia (APL) patients before and after all trans-retinoic acid (ATRA)-based differentiation therapy. Progressive NR4A3 downregulation was coincident with impairments in differentiation in patients during progression to blastic phase of CML, and NR4A3 expression was increased in APL patients treated with ATRA-based differentiating therapy. Together, our findings demonstrate a tight association between impaired differentiation status and NR4A3 downregulation in myeloid leukemias, providing a plausible mechanistic explanation of how myeloid leukemogenesis might occur upon concurrent downregulation of NR4A1 and NR4A3.
Asunto(s)
Leucemia Mielógena Crónica BCR-ABL Positiva , Leucemia Mieloide Aguda , Leucemia Promielocítica Aguda , Receptores de Esteroides , Diferenciación Celular/genética , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Regulación hacia Abajo , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/tratamiento farmacológico , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Promielocítica Aguda/tratamiento farmacológico , Receptores de Esteroides/genética , Receptores de Esteroides/metabolismo , Receptores de Esteroides/uso terapéutico , Receptores de Hormona Tiroidea/genética , Receptores de Hormona Tiroidea/metabolismo , Receptores de Hormona Tiroidea/uso terapéutico , Tretinoina/farmacologíaRESUMEN
Biofilters do not provide much water for bacteria to grow. To use them efficiently and properly, it is essential to understand the kinetics of water transformation and to control moisture levels. This study aims to clarify whether the metabolism of microorganisms will improve the water-holding capacity of media or will intensify drying. This experiment was conducted in duplicate, that is, both with and without bacterial inoculation. Both the constant water content mode and the declining water content mode show that microbial growth in a log phase will enhance drying. In contrast, the bacteria growing in a logarithmic decline phase will improve water-holding capacity. Basically, water evaporation can result from the latent heat obtained from microbial respiration or from the physical temperature difference between the unsaturated air and the wet media. Two ways that biofilters can gain water are from water incorporated into bacteria cells and from water obtained from the oxidation of volatile organic compounds (VOCs).