Key Points• A comprehensive study of 19 gene mutations and their cooperation, including the first report of ASXL1 and TET2 mutations in pediatric AML.• The development of pediatric AML requires fewer gene mutations than adult AML.Gene mutations involving epigenetic regulators recently have been described in adult acute myeloid leukemia (AML). Similar studies are limited in children. We analyzed gene mutations and cooperation in pediatric AML with special reference on mutated epigenetic regulators. Nineteen gene mutations, including 8 class I genes, 4 class II genes, WT1 and TP53 (class III), and 5 epigenetic regulator genes (class IV), were analyzed in 206 children with de novo AML. Mutational analysis was performed with polymerase chain reaction2 based assay followed by direct sequencing. One hundred seventeen of 206 patients (56.8%) had at least one mutation: 51% class I, 13% class II, 6.8% class III, and 5.6% class IV. FLT3-internal tandem duplication was most frequent, and 29% of patients had more than one gene mutation. Two patients carried ASXL1 mutations, both with t(8;21), 2 had DNMT3A mutations, 2 had IDH1 mutations, 1 had IDH2 mutation, and 3 had TET2 mutations. Both patients with IDH1 mutations had AML-M0 subtype and MLL-partial tandem duplication. Cooperating mutations with mutated epigenetic regulators were observed in 8 of 10 patients. We conclude that mutated epigenetic regulators were much less than those in adult AML but with frequent cooperating mutations. ASXL1, TET2, and IDH1 mutations were associated with specific genetic subtypes. (Blood. 2013;121(15):2988-2995 IntroductionComprehensive analyses in de novo childhood acute myeloid leukemia (AML) of gene mutations involving epigenetic regulators have been limited. The ASXL1 (additional sex comb-like 1) gene mapping to chromosome 20q acts as a cofactor of retinoic acid receptor via binding to steroid receptor coactivation-1 and belongs to enhancer of trithorax and polycomb genes that can both activate and repress the HOX gene.1,2 Very recently, it has been demonstrated that ASXL1 loss-of-function mutations result in the loss of polycomb repressive complex 22mediated histone H3 lysine 27 trimethylation, which promotes myeloid leukemia transformation.3 ASXL1 mutations conferred a poor outcome in adult AML, 4,5 but there have been no reports of ASXL1 mutations in childhood AML. TET proteins encode a-ketoglutarate-dependent oxygenases, which are involved in the conversion of 5-methylcytosine to 5-hydroxymethylcytosine. 6 TET2 protein is important for normal myelopoiesis, and disruption of TET2 enzymatic activity results in altered DNA methylation and favors myeloid neoplasm transformation.7 IDH1 and IDH2 mutations convert a-ketoglutarate to 2-hydroxyglutarate, which disrupts TET2 function. 8,9 Somatic mutations of TET2 were identified with microdeletion at 4q24 in myeloid neoplasms by the use of high-resolution single-nucleotide polymorphism microarrays.10,11 TET2 mutations were detected in adult AML with a frequency ranging from 7% to 23%, but t...

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Intestinal parasitic infections are very severe among school aged children in the urban slums, thus regular mass de-worming programs, health education, and the provision of safe drinking water is recommended to combat IPIs among the school aged children.

patient was then discharged to the owner and, at 2, 6, and 12 wk, followed up with orthopedic assessment, owner questionnaire, X-ray imaging, and force-plate gait analysis. RESULTS:Porcine ADSCs expressed mesenchymal stem cell markers CD90 and CD105. Injection of porcine ADSCs into canine stifle joints did not cause any inflammatory or allergic reactions. Orthopedic evaluation found improvements in two dogs, particularly at the longest time point. Owners' evaluation found increased capacity and decreased pain in all three dogs' activities such as walking and running. Radiographic evaluation did not find statistically significant differences before and after treatment. Force-plate analysis found significant improvements in all three dogs after treatment. CONCLUSION:Xenotransplantation of ADSCs for the treatment of OA is feasible. Further studies are needed to validate this novel treatment modality, which can then be implemented for the routine treatment of OA in veterinary medicine. METHODS:To enroll in this study dogs must have stifle joint OA that had lasted ≥ 3 mo and been treated with OA medication without significant improvement. Three dogs fulfilled these criteria and were thus subjects for ADSCs treatment. ADSCs were isolated from abdominal adipose tissue of a 2-mo-old female Yorkshire pig. Their stem cell marker expression was examined by immunofluorescence staining. For treatment, 5 million ADSCs were injected into the diseased joint of each dog. In the next 48 h, the patient was observed for signs of inflammatory and allergic reactions. The