title: Glycogen Synthase Kinase-3β (GSK-3β) and Nuclear Factor Kappa-B (NFKB) in Childhood Acute Lymphoblastic Leukemia.
abstract: BACKGROUND
  Acute lymphocytic leukemia (ALL) is the most common hematologic malignancy in early childhood. In children with acute lymphoblastic leukemia (ALL), the activity of glycogen synthase kinase (GSK-3β) has been associated with changes in the transcriptional activity and expression of nuclear factor kappa beta (NFKB) in the mononuclear cells of bone marrow.
  
  
  OBJECTIVE
  The aim of the study was to determine the possible role of glycogen synthase kinase 3beta (GSK-3β) and nuclear factor kappa beta (NFKB) as prognostic variables in pediatric patients with ALL.
  
  
  METHODS
  This was a descriptive, transversal, and observational study. Bone marrow and blood samples were obtained from 30 children with newly-diagnosed ALL, who were seen at the Hematology-Oncology Service, Hospital para el Niño (HPN), Toluca, Mexico, from 2014‒2015. Anthropometric variables, clinical lab results, immunophenotype and cytogenetic abnormalities were registered. GSK-3β was evaluated through immunohistochemistry, and NFKB messenger RNA (mRNA) with real-time polymerase chain reaction (qPCR). The cases of ALL were classified into two groups of risk: high and habitual.
  
  
  RESULTS
  Thirty patients were included in this study, with a mean age of 7.1 years (range 2‒13 years). Twenty-one were male and 9 female. Employing the morphological classification, 26 patients had type L1 ALL and the remaining 4 patients had type L2 ALL. Abnormal genes were found in 7 (23.33%) patients, ETV-RUNX1 in 3, followed by TCF3-PBX1 (two), STL1-TAL1 (one), and BCR-ABL1 (one). NFKB relative expression levels, in comparison to the GSK-3β immunohistochemistry results of the bone marrow samples, showed significant differences between positive and negative cases (p = 0.001) and between weak-positive and negative cases (p = 0.002).
  
  
  CONCLUSIONS
  These results suggest that GSK-3β may be a prognostic biomarker in childhood ALL.
authors.affiliation: School of Medicine, Autonomous University of the State of Mexico, Toluca, Mexico.
authors.forename: Cristian Fabian Layton
authors.initials: CF
authors.lastname: Tovar
authors.affiliation: Latin American Scientific Association and Ciprés Medical Group, Toluca, Mexico.
authors.forename: Hugo Mendieta
authors.initials: HM
authors.lastname: Zerón
authors.affiliation: Medical Sciences Research Center, Autonomous University of the State of Mexico, Toluca, Mexico.
authors.forename: Maria Del Socorro Camarillo
authors.initials: MD
authors.lastname: Romero
authors.affiliation: Terranova University, Toluca, México.
authors.forename: Yanko V Fabila
authors.initials: YV
authors.lastname: Sánchez
authors.affiliation: Hematology and Oncology Service, The Children's Hospital, Maternal Child of the State of Mexico Institute, Toluca, Mexico.
authors.forename: Isidoro Tejocote
authors.initials: IT
authors.lastname: Romero
mesh_terms: D000293:Adolescent; D014408:Biomarkers, Tumor / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D016328:NF-kappa B; D000071679:Glycogen Synthase Kinase 3 beta
keywords: GSK-3β; NFKB; acute lymphoblastic leukemia; prognostic