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Published on: December 4, 2018
Glycogen Synthase Kinase-3β (GSK-3β) and Nuclear Factor Kappa-B (NFKB) in Childhood Acute Lymphoblastic Leukemia
Cristian Fabian Layton Tovar1, Hugo Mendieta Zerón2, Maria Del Socorro Camarillo Romero3
1School of Medicine, Autonomous University of the State of Mexico, Toluca, Mexico.
Insights
Glycogen synthase kinase 3beta (GSK-3β) and nuclear factor kappa beta (NFKB) may serve as prognostic biomarkers in pediatric acute lymphocytic leukemia (ALL). This study found significant differences in NFKB expression related to GSK-3β activity in bone marrow samples.
Area of Science:
- Pediatric Hematology
- Oncology Research
- Molecular Biology
Background:
- Acute lymphocytic leukemia (ALL) is a common childhood cancer.
- Glycogen synthase kinase 3beta (GSK-3β) activity is linked to nuclear factor kappa beta (NFKB) expression in pediatric ALL.
- Understanding these markers could improve prognostic assessments.
Purpose of the Study:
- To investigate the prognostic significance of GSK-3β and NFKB in pediatric ALL.
- To correlate GSK-3β activity and NFKB expression with disease characteristics.
Main Methods:
- Observational study of 30 newly-diagnosed pediatric ALL patients.
- Analysis of bone marrow and blood samples using immunohistochemistry for GSK-3β and qPCR for NFKB mRNA.
- Classification of ALL cases into high and habitual risk groups.
Main Results:
- NFKB relative expression showed significant differences based on GSK-3β immunohistochemistry results (p = 0.001 for positive vs. negative, p = 0.002 for weak-positive vs. negative).
- Genetic abnormalities were identified in 23.33% of patients.
- The study included patients aged 2-13 years, with a majority being male.
Conclusions:
- GSK-3β shows potential as a prognostic biomarker in childhood ALL.
- Further research is warranted to validate GSK-3β and NFKB as reliable prognostic indicators.
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.
Objectives:
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.
Material And 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.
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