RUNX3 is oncogenic in natural killer/T-cell lymphoma and is transcriptionally regulated by MYC.

RUNX3, runt-domain transcription factor, is a master regulator of gene expression in major developmental pathways. It acts as a tumor suppressor in many cancers but is oncogenic in certain tumors. We observed upregulation of RUNX3 mRNA and protein expression in nasal-type extranodal natural killer (NK)/T-cell lymphoma (NKTL) patient samples and NKTL cell lines compared to normal NK cells. RUNX3 silenced NKTL cells showed increased apoptosis and reduced cell proliferation. Potential binding sites for MYC were identified in the RUNX3 enhancer region. Chromatin immunoprecipitation-quantitative PCR revealed binding activity between MYC and RUNX3. Co-transfection of the MYC expression vector with RUNX3 enhancer reporter plasmid resulted in activation of RUNX3 enhancer indicating that MYC positively regulates RUNX3 transcription in NKTL cell lines. Treatment with a small-molecule MYC inhibitor (JQ1) caused significant downregulation of MYC and RUNX3, leading to apoptosis in NKTL cells. The growth inhibition resulting from depletion of MYC by JQ1 was rescued by ectopic MYC expression. In summary, our study identified RUNX3 overexpression in NKTL with functional oncogenic properties. We further delineate that MYC may be an important upstream driver of RUNX3 upregulation and since MYC is upregulated in NKTL, further study on the employment of MYC inhibition as a therapeutic strategy is warranted.

RUNX1 haploinsufficiency results in granulocyte colony-stimulating factor hypersensitivity.

RUNX1/AML1 is among the most commonly mutated genes in human leukemia. Haploinsufficiency of RUNX1 causes familial platelet disorder with predisposition to myeloid malignancies (FPD/MM). However, the molecular mechanism of FPD/MM remains unknown. Here we show that murine Runx1(+/-) hematopoietic cells are hypersensitive to granulocyte colony-stimulating factor (G-CSF), leading to enhanced expansion and mobilization of stem/progenitor cells and myeloid differentiation block. Upon G-CSF stimulation, Runx1(+/-) cells exhibited a more pronounced phosphorylation of STAT3 as compared with Runx1(+/+) cells, which may be due to reduced expression of Pias3, a key negative regulator of STAT3 signaling, and reduced physical sequestration of STAT3 by RUNX1. Most importantly, blood cells from a FPD patient with RUNX1 mutation exhibited similar G-CSF hypersensitivity. Taken together, Runx1 haploinsufficiency appears to predispose FPD patients to MM by expanding the pool of stem/progenitor cells and blocking myeloid differentiation in response to G-CSF.

Mandatory reporting of domestic violence injuries to the police: what do emergency department patients think?

CONTEXT: Laws requiring mandatory reporting of domestic violence to police exist in 4 states. Controversy exists about the risks and benefits of such laws. OBJECTIVE: To examine attitudes of female emergency department patients toward mandatory reporting of domestic violence injuries to police and how these attitudes may differ by abuse status. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional survey conducted in 1996 of 1218 women patients (72.8% response rate) in 12 emergency departments in California (a state with a mandatory reporting law) and Pennsylvania (without such a law). MAIN OUTCOME MEASURES: Opposition to mandatory reporting to police and the characteristics associated with this belief. RESULTS: Twelve percent of respondents (n = 140) reported physical or sexual abuse within the past year by a current or former partner. Of abused women, 55.7% supported mandatory reporting and 44.3% opposed mandatory reporting (7.9% preferred that physicians never report abuse to police and 36.4% preferred physicians report only with patient consent). Among nonabused women, 70.7% (n = 728) supported mandatory reporting and 29.3% opposed mandatory reporting. Patients currently seeing/living with partners (odds ratio [OR], 1.5; 95% confidence interval [CI], 1.1-2.0), non-English speakers (OR, 2.1; 95% CI, 1.4-3.0), and those who had experienced physical or sexual abuse within the last year (OR, 2.2; 95% CI, 1.6-2.9) had higher odds of opposing mandatory reporting of domestic violence injuries. There were no differences in attitudes by location (California vs Pennsylvania). CONCLUSIONS: The efficacy of mandatory reporting of domestic violence to police should be further assessed, and policymakers should consider options that include consent of patients before wider implementation.

An evaluation of a system-change training model to improve emergency department response to battered women.

OBJECTIVES: To evaluate a system-change model of training from the Family Violence Prevention Fund and the Pennsylvania Coalition Against Domestic Violence for improving the effectiveness of emergency department (ED) response to intimate partner violence (IPV). METHODS: An experimental design with outcomes measured at baseline, 9-12, and 18-24 months post-intervention. Twelve hospitals in Pennsylvania and California with 20,000-40,000 annual ED visits were randomly selected and randomly assigned to experimental and control conditions. Emergency department teams (physician, nurse, social worker) from each experimental hospital and a local domestic violence advocate participated in a two-day didactic information and team planning intervention. RESULTS: The experimental hospitals were significantly higher than the control hospitals on a staff knowledge and attitude measure (F = 5.57, p = 0.019), on all components of the "culture of the ED" system-change indicator (F = 5.72, p = 0.04), and in patient satisfaction (F = 15.43, p < 0.001) after the intervention. There was no significant difference in the identification rates of battered women (F = 0.411, p = 0.52) (although the linear comparison was in the expected direction) in the medical records of the experimental and control hospitals. CONCLUSIONS: A system-change model of IPV ED training was effective in improving staff attitudes and knowledge about battered women and in protocols and staff training, as well as patient information and satisfaction. However, change in actual clinical practice was more difficult to achieve and may be influenced by institutional policy.

Ocular decompression retinopathy after resolution of acute primary angle closure glaucoma.

A patient presented with acute primary angle closure glaucoma with markedly elevated intraocular pressure. Two weeks after laser peripheral iridotomy and resolution of the acute attack, the patient was noted to have developed scattered retinal haemorrhages. The haemorrhages resolved over time with no visual sequelae. This is the first reported case of ocular decompression retinopathy after resolution of acute primary angle closure glaucoma.

Prevalence of intimate partner abuse in women treated at community hospital emergency departments.

CONTEXT: The majority of prior studies examining intimate partner abuse in the emergency department (ED) setting have been conducted in large, urban tertiary care settings and may not reflect the experiences of women seen at community hospital EDs, which treat the majority of ED patients in the United States. OBJECTIVE: To determine the prevalence of intimate partner abuse among female patients presenting for treatment in community hospital EDs and describe their characteristics. DESIGN: An anonymous survey conducted from 1995 through 1997 inquiring about physical, sexual, and emotional abuse. SETTING: Eleven community EDs in Pennsylvania and California. PARTICIPANTS: All women aged 18 years or older who came to the ED during selected shifts. MAIN OUTCOME MEASURES: Reported acute trauma from abuse, past-year physical or sexual abuse, and lifetime physical or emotional abuse. RESULTS: Surveys were completed by 3455 (74%) of 4641 women seen. The prevalence of reported abuse by an intimate partner was 2.2% (95% confidence interval [CI], 1.7%-2.7%) for acute trauma from abuse, 14.4% (95% CI, 13.2%-15.6%) for past-year physical or sexual abuse, and 36.9% (95% CI, 35.3%-38.6%) for lifetime emotional or physical abuse. California had significantly higher reported rates of past-year physical or sexual abuse (17% vs 12%, P<.001) and lifetime abuse (44% vs 31%, P<.001) than Pennsylvania. Logistic regression modeling identified 4 risk factors for reported physical, sexual, or acute trauma from abuse within the past year: age, 18 to 39 years (odds ratio [OR], 2.2; 95% CI, 1.7-3.0); monthly income less than $1000 (OR, 1.7; 95% CI, 1.3-2.1); children younger than 18 years living in the home (OR, 2.0; 95% CI, 1.5-2.6); and ending a relationship within the past year (OR, 7.0; 95% CI, 5.5-8.9). CONCLUSION: If the prevalence of abuse in community hospitals throughout the United States is similar to the range of prevalence estimates found in this study, then heightened awareness of intimate partner abuse is warranted for patients presenting to the ED.