AI Article Synopsis
- - SOD2 is important for antioxidant defense, and this study investigates its potential link to genetic instability in Chronic Myeloid Leukemia (CML), specifically how silencing SOD2 affects chromosomal stability in cell lines expressing BCR-ABL mutations.
- - Researchers found that SOD2 silencing led to significant genetic instability in specific chromosomal regions and observed lower SOD2 mRNA levels in CML patients, correlating with increased disease severity indicators like leukocytosis and Sokal score.
- - The study suggests that reduced SOD2 expression may contribute to a mutator phenotype in CML patients undergoing Tyrosine Kinase Inhibitor (TKI) therapies, highlighting the need for further research into
Article Abstract
Manganese Superoxide dismutase 2 (SOD2) plays a crucial role in antioxidant defense but there are no data suggesting its role in genetic instability in CML. We evaluated the effects of SOD2 silencing in human UT7 cell line expressing either non-mutated or T315I-mutated BCR-ABL. Array-CGH experiments detected in BCR-ABL-expressing cells silenced for SOD2 a major genetic instability within several chromosomal loci, especially in regions carrying the glypican family (duplicated) and β-defensin genes (deleted). In a large cohort of patients with chronic myeloid leukemia (CML), a significant decrease of SOD2 mRNA was observed. This reduction appeared inversely correlated with leukocytosis and Sokal score, high-risk patients showing lower SOD2 levels. The analysis of anti-oxidant gene expression analysis revealed a specific down-regulation of the expression of PRDX2 in UT7-BCR-ABL and UT7-T315I cells silenced for SOD2 expression. Gene set enrichment analysis performed between the two SOD2-dependent classes of CML patients revealed a significant enrichment of Reactive Oxygen Species (ROS) Pathway. Our data provide the first evidence for a link between SOD2 expression and genetic instability in CML. Consequently, SOD2 mRNA levels should be analyzed in prospective studies as patients with low SOD2 expression could be more prone to develop a mutator phenotype under TKI therapies.
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| http://dx.doi.org/10.1016/j.bbrc.2018.03.023 | DOI Listing |
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