Objectives. Aim of this analysis was to identify trends that will aid in the prevention of injury. Methods. Our data were collected from 1999 to 2011 during a surveillance program of occupational exposures to blood or other potentially infectious materials in a Dental School by using a standard coded protocol. Results. 63 exposures were reported. 56/63 (89%) percutaneous and 7/63 (11%) mucosal, involving a splash to the eye of the dental care workers (DCW). 25/63 (40%) involved students, 23/63 (36%) DCW attending masters and doctorate, 13/63 (21%) DCW attending as tutors and 2/63 (3%) staff. 45/63 (71%) and 18/63 (29%) occurred respectively during and after the use of the device; of last ones, 1/18 (0.05%) were related to instrument clean-up and 1/18 (0.05%) to laboratory activity, 12/18 (67%) occurred when a DCW collided with a sharp object during the setting, and 4/18 (22%) during other activities. The instrument and the body part most likely involved were needle and finger respectively. The overall exposure rate was 4.78 per 10,000 patient visits. Conclusions Our results may serve as benchmark that Dental Schools can employ to assess their frequency of injury.
Purpose:
The stromal and immune bone marrow (BM) landscape is emerging as a crucial determinant for acute myeloid leukemia (AML). Regulatory T cells (Treg) are enriched in the AML microenvironment, but the underlying mechanisms are poorly elucidated. Here, we addressed the effect of IFNγ released by AML cells in BM Treg induction and its impact on AML prognosis.
Experimental Design:
BM aspirates from patients with AML were subdivided according to IFNG expression. Gene expression profiles in INFγhigh and IFNγlow samples were compared by microarray and NanoString analysis and used to compute a prognostic index. The IFNγ release effect on the BM microenvironment was investigated in mesenchymal stromal cell (MSC)/AML cell cocultures. In mice, AML cells silenced for ifng expression were injected intrabone.
Results:
IFNγhigh AML samples showed an upregulation of inflammatory genes, usually correlated with a good prognosis in cancer. In contrast, in patients with AML, high IFNG expression was associated with poor overall survival. Notably, IFNγ release by AML cells positively correlated with a higher BM suppressive Treg frequency. In coculture experiments, IFNγhigh AML cells modified MSC transcriptome by upregulating IFNγ-dependent genes related to Treg induction, including indoleamine 2,3-dioxygenase 1 (IDO1). IDO1 inhibitor abrogated the effect of IFNγ release by AML cells on MSC-derived Treg induction. In vivo, the genetic ablation of IFNγ production by AML cells reduced MSC IDO1 expression and Treg infiltration, hindering AML engraftment.
Conclusions:
IFNγ release by AML cells induces an immune-regulatory program in MSCs and remodels BM immunologic landscape toward Treg induction, contributing to an immunotolerant microenvironment.
Cristina Papayannidis and Jacopo Nanni contributed equally.Novelty statement: Venetoclax (VEN) and hypomethylating agents (HMAs) regimen is rapidly emerging as the standard of care for unfit-to-chemotherapy acute myeloid leukemia (AML) patients. Hospitalization negatively affects the quality of life of patients with cancer, including AML, and may be associated with more severe complications such as infections. To the best of our knowledge, no data have been reported about the safety and feasibility of a total outpatient management of AML patients following VEN and HMAs regimen. Our real-life study highlights that such approach is feasible without negatively impacting on treatment efficacy and may yield pharmacoeconomic and quality-of-life benefits.
FMS-like tyrosine kinase 3 (FLT3) is among the most common driver genes recurrently mutated in acute myeloid leukemia (AML), accounting for approximately 30% of cases. Activating mutations of the FLT3 receptor include internal tandem duplications (ITD) that map to the auto-inhibitory juxtamembrane (JM) domain or point mutations within the tyrosine kinase domain (TKD). Several FLT3 tyrosine kinase inhibitors have been developed in the last few years, but midostaurin is currently the only one approved for the treatment of newly diagnosed patients harboring FLT3 mutations. Here we describe for the first time a novel in-frame deletion in exon 14 (JM domain) of the FLT3 gene, that we identified in a young woman with CBFb-MYH11-positive AML. We demonstrated that this novel FLT3 variant is pathogenic, since it is responsible for constitutive activation of FLT3 receptor. Finally, ex-vivo studies demonstrated that this novel mutation is sensitive to midostaurin.
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