Mouse anti-Human E12/E47 monoclonal antibody, clone H09-382

Background Preterm birth places infants at higher risk of adverse long-term behavioral and cognitive outcomes. Combining biobehavioral measures and molecular biomarkers may improve tools to predict the risk of long-term developmental delays. Methods The Neonatal Neurobehavior and Outcomes in Very Preterm Infants study was conducted at nine neonatal intensive care units between April 2014 and June 2016. Cries were recorded and buccal swabs collected during the neurobehavioral exam. Cry episodes were extracted and analyzed using a computer system and the data were summarized using factor analysis. Genomic DNA was extracted from buccal swabs, quantified using the Qubit Fluorometer, and aliquoted into standardized concentrations. DNA methylation was measured with the Illumina MethylationEPIC BeadArray, and an epigenome-wide association study was performed using cry factors (n = 335). Results Eighteen CpGs were associated with the cry factors at genome-wide significance (alpha = 7.08E - 09). Two CpG sites, one intergenic and one linked to geneTCF3(important for B and T lymphocyte development), were associated with acoustic measures of cry energy. Increased methylation of TCF3 was associated with a lower energy-related cry factor. We also found that pitch (F-0) and hyperpitch (F-0 > 1 kHz) were associated with DNA methylation variability at 16 CpG sites. Conclusions Acoustic cry characteristics are related to variation in DNA methylation in preterm infants. Impact Preterm birth is a major public health problem and its long-term impact on health is not well understood. Cry acoustics, related to prematurity, has been linked to a variety of medical conditions. Biobehavioral measures and molecular biomarkers can improve prediction tools for long-term developmental risks of preterm birth. Variation in epigenetic modulation in preterm infants provides a potential link between preterm birth and unfavorable developmental outcomes.

Background: JL1 is a newly identified CD43 epitope that specifically recognizes leukemic cells. We analyzed the incidence of JL1 expression and compared the clinical, immunophenotypic, and genetic characteristics of de novo pediatric acute leukemia patients with respect to JL1 expression status to determine the therapeutic potential of an anti-JL1 antibody. Methods: Seventy-eight patients with pediatric acute leukemia (52 with ALL, 26 with AML) diagnosed between December 2014 and January 2016 were enrolled prospectively. Flow cytometry for JL1 expression was performed at diagnosis. Clinical, immunophenotypic, and genetic characteristics were compared with respect to JL1 expression status by the Student t-test/Mann-Whitney U test and chi-square test/Fisher's exact test. Results: The incidence of JL1 expression was 76.9% and 84.6% in ALL and AML patients, respectively. ALL patients with JL1 expression showed higher CD10 and cytoplasmic IgM expressions than those without JL1 expression (P=0.022 and 0.003, respectively) and were associated with TCF3-PBX1 and KMT2A-MLLT1 translocations. AML patients with JL1 expression showed higher CD13 and lower CD65 and CD15 expressions than those without JL1 expression (P=0.013, 0.007, and 0.024, respectively) and were associated with RUNX1-RUNX1T1, PML-RARA, and CBFB-MYH11 translocations. The JL1 expression incidence did not differ between ALL and AML, and the JL1 expression status did not affect prognosis. Conclusions: Our findings support the potential therapeutic role of anti-JL1 monoclonal antibodies; JL1 expression was associated with specific immunophenotypes and genetic abnormalities. Future studies should examine the prognostic impact of JL1 expression in pediatric acute leukemias.