RESUMEN

Acute myeloid leukemia (AML) is maintained by self-renewing leukemic stem cells (LSCs). A fundamental problem in treating AML is that conventional therapy fails to eliminate LSCs, which can reinitiate leukemia. Heat shock transcription factor 1 (HSF1), a central regulator of the stress response, has emerged as an important target in cancer therapy. Using genetic Hsf1 deletion and a direct HSF1 small molecule inhibitor, we show that HSF1 is specifically required for the maintenance of AML, while sparing steady-state and stressed hematopoiesis. Mechanistically, deletion of Hsf1 dysregulates multifaceted genes involved in LSC stemness and suppresses mitochondrial oxidative phosphorylation through downregulation of succinate dehydrogenase C (SDHC), a direct HSF1 target. Forced expression of SDHC largely restores the Hsf1 ablation-induced AML developmental defect. Importantly, the growth and engraftment of human AML cells are suppressed by HSF1 inhibition. Our data provide a rationale for developing efficacious small molecules to specifically target HSF1 in AML.

Asunto(s)

RESUMEN

We describe the heretofore unreported case of an HPV-related carcinoma of the palatine tonsil with distinct areas of squamous cell- and adenoid cystic carcinoma-like differentiation in a 54-year old patient. The morphological, immunophenotypic and molecular findings of the tumor are illustrated. We discuss the parallels between the tumor and HPV-related multiphenotypic sinonasal carcinoma (HMSC) which is well-known to exhibit adenoid cystic carcinoma-like features. A review of the literature of high-risk HPV-associated non-squamous carcinomas of the oropharynx is presented.

Asunto(s)

RESUMEN

HIV-1/2 antigen/antibody (Ag/Ab) immunoassays that detect HIV-1 and HIV-2 antibodies and HIV-1 p24 antigen are commonly used in the diagnosis of HIV-1/HIV-2 infections in human plasma/serum. Samples from patients with positive screening results require confirmation by antibody differentiation and/or HIV PCR assays. HIV screening assays are commonly reported as positive or negative based on a signal-to-cutoff (S/CO) threshold. For some HIV screening assays, the strength of the S/CO value correlates with likelihood that confirmatory testing will be positive. The data in this article provide results from two HIV Ag/Ab combination assays (Abbott Architect HIV Ag/Ab Combo Assay, a 4th generation combination assay; Bio-Rad Bioplex 2200 HIV Ag-Ab Assay, a 5th generation assay). The data include 23,331 HIV screening results, S/CO ratios, antibody differentiation or Western blot results (for samples with positive HIV screens), HIV-1 PCR results (if performed), patient location at time of testing, age, and sex. Distribution of S/CO ratios for the Bio-Rad HIV screening assay data and the distribution of S/CO values for samples with positive screening results were analyzed.

RESUMEN

Hemangiomas are the most common benign lesions involving the spine. Metastasis is the most common malignant condition. The diagnosis of typical hemangiomas on conventional CT and MRI imaging is straightforward. However, when the hemangiomas are very large they may have atypical features making their diagnosis on these conventional imaging modalities inconclusive. In such cases nuclear medicine techniques such as Tc-99m RBC may aid in resolving the diagnostic conundrum. Awareness and use of proper diagnostic modality can prevent unnecessary biopsy. In this case report we try to highlight the added value of Tc-99m RBC scan to conventional imaging techniques in differentiating giant vertebral hemangioma from more aggressive malignant tumors.

RESUMEN

Daylight saving time is a practice in some countries and local regions to set clocks forward (typically 1 hour) during the longer days of summer and back again in autumn. Time changes resulting from daylight saving time have the potential to impact clinical laboratory instruments, computer interfaces, and information systems. We analyzed turnaround time data for an academic medical center clinical laboratories (chemistry, hematology, blood gas analyzer, and transfusion medicine), examining how turnaround time was impacted by the daylight saving time shifts in 2017. We also determined whether the daylight saving time shift on November 5, 2017 ("fall back" by 1 hour) resulted in any "absurd" time combinations such as a receipt time occurring "before" a normally later time such as final result. We also describe challenges resulting from daylight saving time changes over a 5-year period. The only significant impact on turnaround time was for clinical chemistry samples during the autumn daylight saving time change, but the overall impact was low. Four instances of absurd time combinations occurred in the autumn time change with only a transfusion medicine example resulting in an interface error (a Type and Screen resulted "before" receipt in laboratory). Over a 5-year period, other daylight saving time impacts included problems of reestablishing interface to instruments, inadvertent discrepancies in manual time changes at different points of the core laboratory automation line, and time change errors in instruments with older operating systems lacking patches that updated daylight saving time rules after 2007. Clinical laboratories should be aware that rare problems may occur due to issues with daylight saving time changes.