t(12;21)(p13;q22)[ETV6-RUNX1] is the most common chromosomal translocation in childhood acute lymphoblastic leukemia, and it can often be backtracked to Guthrie cards supporting prenatal initiation and high levels of circulating t(12;21)-positive cells at birth. To explore the prevalence of ETV6-RUNX1-positive cells in healthy neonates, mononuclear cells from 1417 umbilical cord blood samples were isolated within 24 hours from birth and subsequently screened for ETV6-RUNX1 transcripts using a highly sensitive real-time reverse transcription polymerase chain reaction assay. In first-run polymerase chain reaction, 14 samples were positive at levels below 10 ؊5 , of which specific hybridization reflecting the relevant genetic region was positive in 9 cases. Repeated analyses using stored mRNA and flowcytometric sorting of a CD19 ؉ , CD8 ؉ , and CD19 ؊ /CD8 ؊ subpopulations from cryopreserved mononuclear cells from the same cord blood samples (mean sorted: 18 ؋ 10 6 cells) revealed no positive findings, which demonstrates that the level and/or frequency of ETV6-RUNX1-positive cells is markedly lower than suggested in previous studies. IntroductionThe development of childhood B-cell lineage acute lymphoblastic leukemia (ALL) involves (at least) 2 genetic events (hits), 1 the first of which frequently arises prenatally. [2][3][4][5][6][7][8][9][10][11] Unless the postnatal genetic hit(s) is inevitable, the prevalence of newborns harboring preleukemic first hit-cells should exceed the cumulative incidence of the corresponding leukemia. Accordingly, gene transcripts from the most common childhood ALL chromosomal translocation, t(12;21)(p13;q22)[ETV6-RUNX1], were demonstrated in approximately 1% of healthy newborns in one British study, 12 corresponding to 100-fold the cumulative incidence of ETV6-RUNX1-positive ALL in childhood. 13 Noteworthy, the positive cells were reported to occur at levels of 10 Ϫ3 -10 Ϫ4 , and a threshold of 10 Ϫ5 was used for classification of t(12;2)-positive samples with no report of subthreshold frequencies. 12 Since these results are important for mapping the natural history of t(12;21)-positive ALL and furthermore limits the options for future screening, we assessed the prevalence of ETV6-RUNX-positive cells in 1417 newborns. MethodsMononucleated cells (MNCs) were isolated from umbilical cord blood (UCB) samples from healthy, full-term newborns through Ficoll density centrifugation 14 within 24 hours after birth to minimize cellular and/or mRNA degradation. 15 This study was approved by the Danish Data Protection Agency and the Danish Scientific Ethics Committee.mRNA from Ն 2.5 ϫ 10 6 MNCs was extracted using a KingFisher mL robot (ThermoFisher) and the MagAttrackDirect mRNA-M48 Kit (QIAGEN): 750 L of lysis solution, 75 L of magnetic beads, and 550 L of washing solution IϩII. mRNA was eluted in 50 L of RNase-free water, divided into 2 tubes, and stored at Ϫ80°C until use. Surplus MNCs were cryopreserved in liquid nitrogen. For subsequent flow cytometrically sorted subpopulations, mRNA was c...

The pattern of infections in the first years of life modulates our immune system, and a low incidence of infections has been linked to an increased risk of common childhood acute lymphoblastic leukemia (ALL). We here present a new interpretation of these observations -the adrenal hypothesis -that proposes that the risk of childhood ALL is reduced when early childhood infections induce qualitative and quantitative changes in the hypothalamus-pituitary-adrenal axis that increase plasma cortisol levels. This may directly eliminate leukemic cells as well as preleukemic cells for the ALL subsets that dominate in the first 5-7 years of life and may furthermore suppress the Th1-dominated proinflammatory response to infections, and thus lower the proliferative stress on preexisting preleukemic cells.

In this large population-based cohort study, anaesthesia care with TI was not different from anaesthesia care without airway instrumentation in patients undergoing emergency OGD in terms of 90 day mortality and length of hospital stay.

The absence of association between hospitalisation for infections and risk of childhood ALL directs future investigations of the role of infections in development of childhood ALL towards exploration of less severe infections.