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Altered Expression of Ribosome Biogenesis Regulators (TP53, C-MYC, FBL, and NCL) in Precursor B-cell Acute
Michalina Horochowska1, Dawid Przystupski1, Marta Kamińska2
1Department of Pediatric Bone Marrow Transplantation, Oncology and Hematology, Wroclaw Medical University, 50-556 Wrocław, Poland.
Background/Objectives:
Rapid cellular proliferation, a hallmark of malignancy, requires sustained and elevated protein synthesis, which in turn requires efficient ribosome biogenesis. The aim of this study was to evaluate the expression levels of TP53, C-MYC, FBL, and NCL in pre-B ALL and neuroblastoma tissues compared to healthy bone marrow samples-factors that may carry prognostic significance in pediatric malignancies.
Materials And Methods:
The cohort included 45 pre-B ALL patients, 19 neuroblastoma patients, and 12 healthy bone marrow donors as controls. Total RNA was extracted from bone marrow or tumor samples and cDNA synthesis was performed with the Bio-Rad iScript kit. Quantitative PCR was conducted using SYBR Green chemistry, with GAPDH as the reference gene. Primers targeted TP53, C-MYC, FBL, and NCL, and gene expression was calculated using the 2-ΔCt method.
Results:
The expression of C-MYC and FBL was found to be significantly decreased in patients with pre-B ALL in comparison to the healthy control group. NCL expression was highest in healthy donors, intermediate in pre-B ALL, and lowest in neuroblastoma. In addition to intergroup comparisons, correlations between gene expression levels were assessed within each diagnostic group. In the pre-B ALL group, a positive correlation was observed between TP53 and C-MYC expression, as well as between TP53 and both FBL and NCL. Furthermore, a significant positive correlation was found between FBL and NCL. In the neuroblastoma group, a statistically significant positive correlation was identified between C-MYC and FBL expression. In the control group, TP53 expression was positively correlated with NCL, and FBL expression showed a significant positive correlation with NCL.
Conclusions:
This study suggests the altered expression of ribosome biogenesis-related genes in pediatric pre-B acute lymphoblastic leukemia and neuroblastoma. The reported dysregulation suggests a disease-associated disruption in nucleolar function and translational regulation and may contribute to oncogenesis through altered ribosomal assembly, protein synthesis, or proliferative signaling.
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