Here we demonstrate that Meis1, a TALE family homeodomain GSK690693 concentration transcription factor involved in numerous embryonic developmental processes, is selectively expressed in hematopoietic stem/progenitor cells. Conditional Meis1 knockout in adult hematopoietic cells resulted in a significant reduction in the hematopoietic stem/progenitor cells. Suppression of hematopoiesis by Meis1 deletion appears to be caused by impaired self-renewal activity and reduced cellular quiescence of hematopoietic stem/progenitor cells in a cell autonomous manner, resulting in stem cell exhaustion and defective long-term hematopoiesis. Meis1 deficiency down-regulated
a subset of Pbx1-dependent hematopoietic stem cell signature genes, suggesting a functional link between them in the maintenance of hematopoietic stem/progenitor cells. These results show the importance of Meis1 in adult hematopoiesis.”
“Objectives: To explore the potential prognostic significance of the lymphocyte-monocyte ratio (LMR) in patients with nonmetastatic renal cell carcinoma (RCC), as the LMR has been repeatedly proposed to have a negative effect LY2157299 ic50 on patient’s survival in various hematological and solid cancers. However, findings about LMR’s prognostic significance in RCC have not been reported yet. Methods
and materials: We retrospectively evaluated the prognostic significance of the LMR in a cohort comprising 678 patients with nonmetastatic clear cell RCC, who were operated between 2000 and 2010 with curative radical or partial nephrectomy at a single tertiary academic center. Preoperative LMR was calculated 1 day before surgical intervention. Patients were categorized using an LMR cutoff of 3.0. Cancer-specific survival (CSS), metastasis-free survival, and overall survival were assessed using the Kaplan-Meier method. To evaluate the independent prognostic significance of the LMR, multivariate Cox
regression models were applied. Additionally, the influence of the LMR on the predictive accuracy of Selonsertib the Leibovich prognosis score was determined using the Harrell concordance index (c-index) and decision curve analysis. Results: Low LMR was statistically significantly associated with older patients ( bigger than = 65 y), high tumor grade (G3 + G4), advanced pathologic T category (pT3 + pT4), the presence of histologic tumor necrosis, and male gender (P smaller than 0.05). Multivariate analysis identified a low LMR as an independent prognostic factor for patients’ CSS (hazard ratio = 2.33; 95% CI: 1.10-4.94; P = 0.027). The estimated c-index was 0.83 using the Leibovich prognosis score and 0.86 when the LMR was added. Conclusions: Regarding CSS of patients with RCC, a decreased LMR represents an independent prognostic factor. Adding the LMR to well-established prognostic models, such as the Leibovich prognosis score, might improve their predictive ability. (C) 2014 Elsevier Inc.