Nuclear factor I-C overexpression promotes monocytic development and cell survival in acute myeloid leukemia

Nuclear factor I-C (NFIC) belongs to a family of NFI transcription factors that binds to DNA through CAATT-boxes and are involved in cellular differentiation and stem cell maintenance. Here we show NFIC protein is significantly overexpressed in 69% of acute myeloid leukemia patients. Examination of the functional consequences of NFIC overexpression in HSPCs showed that this protein promoted monocytic differentiation. Single-cell RNA sequencing analysis further demonstrated that NFIC overexpressing monocytes had increased expression of growth and survival genes. In contrast, depletion of NFIC through shRNA decreased cell growth, increased cell cycle arrest and apoptosis in AML cell lines and AML patient blasts. Further, in AML cell lines (THP-1), bulk RNA sequencing of NFIC knockdown led to downregulation of genes involved in cell survival and oncogenic signaling pathways including mixed lineage leukemia-1 (MLL-1). Lastly, we show that NFIC knockdown in an ex vivo mouse MLL::AF9 pre-leukemic stem cell model, decreased their growth and colony formation and increased expression of myeloid differentiation markers Gr1 and Mac1. Collectively, our results suggest that NFIC is an important transcription factor in myeloid differentiation as well as AML cell survival and is a potential therapeutic target in AML

Nuclear factor I-C overexpression promotes monocytic development and cell survival in acute myeloid leukemia

Nuclear factor I-C (NFIC) belongs to a family of NFI transcription factors that binds to DNA through CAATT-boxes and are involved in cellular differentiation and stem cell maintenance. Here we show NFIC protein is significantly overexpressed in 69% of acute myeloid leukemia patients. Examination of the functional consequences of NFIC overexpression in HSPCs showed that this protein promoted monocytic differentiation. Single-cell RNA sequencing analysis further demonstrated that NFIC overexpressing monocytes had increased expression of growth and survival genes. In contrast, depletion of NFIC through shRNA decreased cell growth, increased cell cycle arrest and apoptosis in AML cell lines and AML patient blasts. Further, in AML cell lines (THP-1), bulk RNA sequencing of NFIC knockdown led to downregulation of genes involved in cell survival and oncogenic signaling pathways including mixed lineage leukemia-1 (MLL-1). Lastly, we show that NFIC knockdown in an ex vivo mouse MLL::AF9 pre-leukemic stem cell model, decreased their growth and colony formation and increased expression of myeloid differentiation markers Gr1 and Mac1. Collectively, our results suggest that NFIC is an important transcription factor in myeloid differentiation as well as AML cell survival and is a potential therapeutic target in AML

Patients’ Satisfaction and Oral Health-Related Quality of Life of Edentulous Patients Using Conventional Complete Dentures and Implant-Retained Overdentures in Saudi Arabia

The aim of this study was to compare patients’ satisfaction and quality of life (QoL) when using implant overdentures vs. conventional dentures. The QoL of Saudi patients who were provided mandibular implant-supported overdentures was assessed using a structured questionnaire. Overall satisfaction; ability to speak, eat, and chew food; comfort; esthetics; stability; and satisfaction of general oral health were measured. A total of 48.3% vs. 6.9% were, overall, very satisfied with their implant overdentures and conventional dentures, respectively. A total of 37.9% of the patients were very satisfied regarding speaking with their implant overdentures vs. 17.2% with conventional dentures. Furthermore, 41.4% were very comfortable with their implant overdentures vs. 5.2% were very comfortable using conventional dentures. However, only 15.5% were very satisfied with the esthetics of the conventional dentures compared to 43.1% being satisfied with implant overdentures. Only 1.7% were very satisfied with the stability of conventional dentures vs. 44.8% being satisfied using implant overdentures. About 8.6% of the candidates were very satisfied regarding chewing food with conventional dentures vs. 36.2% being very satisfied using implant overdentures. Approximately 10.3% were very satisfied with their general oral health using conventional dentures compared to 29.3% being very satisfied using implant overdentures. Mandibular implant overdentures had a strong impact on patients’ quality of life over conventional complete dentures and should be considered the minimum standard of care provided to completely edentulous patients