Subclonal TP53 and KRAS variants combined with poor treatment response identify ultra-high-risk pediatric T-ALL patients.

Variations in the TP53 and KRAS genes indicate a particularly adverse prognosis in relapsed pediatric T-ALL. We hypothesized that these variations might be subclonally present at disease onset and contribute to relapse risk. To test this, we examined two cohorts of children diagnosed with T-ALL: one with 81 patients who relapsed and 79 matched non-relapsing controls, and another with 226 consecutive patients, 30 of whom relapsed.

Inhibiting H3K27 Demethylases Downregulates CREB-CREBBP, Overcoming Resistance in Relapsed Acute Lymphoblastic Leukemia.

Background: CREB binding protein (CREBBP) is a key epigenetic regulator, altered in a fifth of relapsed cases of acute lymphoblastic leukemia (ALL). Selectively targeting epigenetic signaling may be an effective novel therapeutic approach to overcome drug resistance. Anti-tumor effects have previously been demonstrated for GSK-J4, a selective H3K27 histone demethylase inhibitor, in several animal models of cancers.

Serially Quantifying TERT Rearrangement Breakpoints in ctDNA Enables Minimal Residual Disease Monitoring in Patients with Neuroblastoma.

Real-time molecular monitoring of TERT-rearranged high-risk neuroblastoma is an unmet clinical need. We tested liquid biopsy-based assays for patient-individualized TERT breakpoint sequences to monitor disease in pediatric patients. Our digital PCR approach provides high resolution of spatial and temporal disease quantification in individual patients and is applicable for clinical routine.

Prospective Evaluation of Lung Cancer Screening Eligibility Criteria and Lung Cancer Detection in the Yorkshire Lung Screening Trial.

Introduction: Low-dose computed tomography screening for lung cancer reduces lung cancer mortality, but there is a lack of international consensus regarding the optimal eligibility criteria for screening. The Yorkshire Lung Screening Trial was designed to evaluate lung cancer screening (LCS) implementation, and a primary objective was prospective evaluation of three predefined eligibility criteria.

Methods: Individuals who had ever smoked, aged 55 to 80 years, who responded to written invitation, underwent telephone risk assessment and if eligible by at least one criterion (PLCO ≥ 1.

[Nephritic sediment - step by step].

The examination of urine and its evaluation are central components in the diagnostic pathway for kidney diseases. Essential to this process is the correct analysis and interpretation of the urine sediment. A nephritic sediment indicates glomerular kidney disease with high specificity.