Objectives To determine the prevalence of antibodies to SARS-CoV-2 and the incidence of seroconversion in the first month of follow-up among interns, residents, and medical doctors attending patients at a University Hospital, to explore for associations of seroprevalence and seroconversion with risk factors and symptoms compatible with COVID-19, and to explore the concordance of CLA, LFA, and ELFA. Design or methods We conducted a cross-sectional and a prospective study among medical doctors and medical trainees at Hospital Universitario San Ignacio in Bogota (Colombia) during June, July, and August to assess seroprevalence and seroconversion rates in this population was performed using CLA IgG for SARS-CoV-2. LFA IgG and IgM and ELFA IgM were also determined to explore concordance with CLA IgG. Results At baseline, 8 (2.28% 95%CI 1.16-4.43%) individuals were IgG positive for SARS-CoV-2 by CLA. At the end of the study, 21 (5.98% 95%CI 3.94-8.97%) individuals seroconverted by CLA IgG. In all, 29 individuals had IgG by CLA and of these 11 (3.13% 95%CI 1.76-5.52%) were asymptomatic. No associations with risk factors for infection were identified. CLA had moderate concordance with LFA IgG and ELFA, but minimal with LFA IgM. Conclusions Our report is one of the first in Latina America on seroprevalence and seroconversion rates in medical healthcare workers. It emphasizes the importance of avoiding focusing only on symptomatic individuals to screen this population for SARS-CoV-2 infection, since of all individuals that have evidence of previous infection many (37.93%) may be pre-symptomatic or asymptomatic and may contribute to infection/disease spread.
Although B-cell acute lymphoblastic leukemia (B-cell ALL) survival rates have improved in recent years, Hispanic children continue to have poorer survival rates. Our aim was to identify biomarkers of treatment response, which may also predict relapse and death, through identifying differentially expressed and methylated genes between patients who responded or did not respond to induction treatment. DNA methylation and mRNA sequencing assays were performed on 27 bone marrows from Hispanic children with B-cell ALL. Gene expression and differential methylation were compared between responders and non-responders at day 15 and at the end of induction chemotherapy. DAPK1, CNKSR3, MIR4435-HG2, CTHRC1, NPDC1, SLC45A3, ITGA6, and ASCL2 were overexpressed and hypomethylated in non-responders. The overexpression of DAPK1, ASCL2, SCL45A3, NPDC1 and ITGA6 can predict non-response at day 15 and refractoriness. Additionally, higher expression of MIR4435-2HG increases the probability of non-response, death, and the risk of death. MIR4435-2HG is also overexpressed in relapse samples. Finally, MIR4435-2HG overexpression, together with positive minimal residual disease, are associated with poorer survival, and together with overexpression of DAPK1 and ASCL2, it could improve the risk classification of patients with normal karyotype. MIR4435-2HG is a potential predictive biomarker in children with B-cell ALL.
Acute lymphoblastic leukemias (ALL) are the most common hematopoietic neoplasms in children. Survival in developed countries is >80%, while in Colombia is ≤60%. These differences have been related to different factors, including genetic and epigenetic alterations, which could regulate chemoresistance mechanisms. Currently, some genetic alterations have been used to classify patients in a risk group, but a genetic profile that can be applicable to most patients to predict with high sensitivity the response to induction chemotherapy, improve the risk classification and predict survival is highly needed. We aim to identify gene profiles associated with response to induction chemotherapy in pediatric patients with ALL-B. Methods: Bone marrow samples were collected from 27 patients with a new diagnosis of B-ALL. Blasts were separated and purified according to the expression of the CD19 and CD34. RNA was extracted and used as template for genomic libraries. RNA-seq was done using the Illumina platform, and the reads were aligned and quantified using Partek Flow. DEseq2 was used for statistical analysis and to determine the differentially expressed genes (DEG) between the patient groups. Response to induction treatment was defined (flow cytometry) as positive or negative minimal residual disease (MRD) as percentage of residual blasts >0.01% or <0.01%, respectively. Three comparison groups were defined: 1) true responders (MRD- at day 15 and MRD- at the end of induction) vs. true non-responders (MRD+ at day 15, and MRD + at the end of induction), 2) MRD- vs MRD+ at the 15 day of induction; 3) MRD- vs MRD+ at the end of induction. Genes with a p <0.05 and a fold change >2 were chosen. Additionally, an enrichment analysis was performed to determine the signaling pathways associated with treatment response. Results: 159 DEGs were found among MRD- vs MRD+ at day 15 of the induction, 200 DEGs were identified between MRD- vs. MRD+ at the end of induction, and 153 DEGs were found between patients classified as true responders vs. true non-responders. Additionally, to determine the genes that could be predicting the response to treatment, a comparison was made between the DEGs of each group of patients analyzed, finding 50 genes in common. Interestingly, the genes identified are associated with differentiation of stem cells (HOXB2), metabolic process (ST8SIA6, SPHK1, HPGD), immune response (CFH, PAR2, NFAM), cell-cell signaling (PEAR1, PTGIR), and ion transmembrane transport (SLC2A7, SLC45A3). The overexpression of these genes is associated with a poor response to induction chemotherapy. Conclusion: We identified 50 genes associated with the response to induction chemotherapy in pediatric patients with ALL-B. Those genes are associated with signaling pathways that could be explaining the lack of response in patients and might serve as possible biomarkers of response to induction treatment. Citation Format: Yulieth X. Torres-Llanos, Jovanny Zabaleta, Nataly Cruz-Rodriguez, Sandra M. Quijano, Paula C. Guzmán, Iliana De Los Reyes, Ana M. Infante, Liliana Lopez, Alba L. Combita. Gene expression profiles associated with induction treatment response in pediatric patients with acute lymphoblastic leukemia type B [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5143.
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