Background: Glutathione (GSH) plays an important role in anti-oxidant defense and detoxification reactions. It is primarily synthesized in the liver by the transsulfuration pathway and exported to provide precursors for in situ GSH synthesis by other tissues. Deficits in glutathione have been implicated in aging and a host of diseases including Alzheimer's disease, Parkinson's disease, cardiovascular disease, cancer, Down syndrome and autism.

GVL against chronic phase CML (CP-CML) is potent, but it is less efficacious against acute leukemias and blast crisis CML (BC-CML). The mechanisms underlying GVL-resistance are unknown. Previously, we found that alloreactive T cell targeting of GVL-sensitive bcr-abl-induced mouse CP-CML (mCP-CML) required TCR:MHC interactions and that multiple and redundant killing mechanisms were in play. To better understand why BC-CML is resistant to GVL, we performed a comprehensive analysis of GVL against mouse BC-CML (mBC-CML) induced by the retroviral transfer of the bcr-abl and NUP98/HOXA9 fusion cDNAs. Like human BC-CML, mBC-CML was GVL-resistant, and this was not due to accelerated kinetics or a greater leukemia burden. To study T cell recognition and killing mechanisms, we generated a panel of gene-deficient leukemias by transducing bone marrow from gene-deficient mice. T cell target recognition absolutely required that mBC-CML cells express MHC and GVL against both mCP-CML and mBC-CML required leukemia expression of ICAM-1. We hypothesized that mBC-CML would be resistant to some of the killing mechanisms sufficient to eliminate mCP-CML, but we found instead that the same mechanisms were effective against both types of leukemia as GVL was similar against wild type or mBC-CML genetically lacking Fas, TRAIL-R, Fas/TRAIL-R, TNFR1/R2 or when donor T cells were perforin−/−. However, mCP-CML but not mBC-CML, relied on expression of PD-ligands to resist T cell killing, as only GVL against mCP-CML was augmented when leukemias lacked PD-L1/L2. Thus, mBC-CML cells have cell-intrinsic mechanisms distinct from mCP-CML cells that protect them from T cell killing.

Key Points Standard chemotherapy can still be used for new diagnosis of acute lymphoblastic leukemia in patients with SARS-CoV-2. Corticosteroid can be given safely to patients with SARS-CoV-2 presenting with acute respiratory distress syndrome and ALL.

Commercially available films minimize the importance of the psychosocial dimension of care, which can perpetuate stigma around psychosocial needs and interventions. These films can be used to encourage discussion about how to optimize psychosocial care in pediatric oncology so that such care is not abandoned in actual practice as it is, for entertainment purposes, on the screen.

Beckwith-Wiedemann syndrome (BWS) is an epigenetic overgrowth disorder and cancer predisposition syndrome caused by imprinting defects of chromosome 11p15.5-11p15.4. BWS should be considered in children with atypical presentations of embryonal tumors regardless of clinical phenotype. Risk of malignancy correlates with specific molecular subgroups of BWS making molecular subclassification important for appropriate cancer screening. We report the first case of concurrent embryonal tumors in a phenotypically normal child, leading to the diagnosis of BWS with paternal uniparental disomy and describe the molecular classification of BWS as it relates to malignancy risk, along with approach to management.