Expression of thioredoxin-1 (TXN) and its relation with oxidative DNA damage and treatment outcome in adult AML and ALL: A comparative study

• Published in: Hematology (Luxembourg) Vol. 21; no. 10; pp. 567 - 575
• Main Authors: Kamal, Amany M., Hamdy, Nadia M., Hegab, Hany M., El-Mesallamy, Hala O.
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 25.11.2016
• Subjects: 8-OHdG; Adult; Aged; ALL; AML; Deoxyguanosine - analogs & derivatives; Deoxyguanosine - blood; DNA Damage; Female; Humans; Leukemia, Myeloid, Acute - blood; Leukemia, Myeloid, Acute - genetics; Leukemia, Myeloid, Acute - metabolism; Leukemia, Myeloid, Acute - pathology; Male; Middle Aged; Oxidative DNA damage; Oxidative Stress - physiology; Precursor Cell Lymphoblastic Leukemia-Lymphoma - blood; Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics; Precursor Cell Lymphoblastic Leukemia-Lymphoma - metabolism; Precursor Cell Lymphoblastic Leukemia-Lymphoma - pathology; Strand breaks; Thioredoxin; Thioredoxins - biosynthesis; Thioredoxins - genetics; Treatment Outcome; TXN; Young Adult; AML; ALL; Strand breaks; TXN; Thioredoxin; 8-OHdG; Oxidative DNA damage
• ISSN: 1607-8454; 1607-8454
• DOI: 10.1080/10245332.2016.1173341

Objective: Thioredoxin-1 (TXN) is a key element in the elimination of reactive oxygen species as well as activation of tumor suppressor genes and DNA repair enzymes. Several studies showed that TXN was over expressed in solid tumors and this was correlated to poorer prognosis. However, TXN expression has been insufficiently studied, particularly in newly diagnosed adult acute leukemia. Methods: This study was designed to evaluate the gene expression of TXN in acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL) adult patients and to investigate its association with oxidative DNA damage. The expression of TXN was analyzed using quantitative reverse transcriptase-polymerase chain reaction while oxidative DNA damage was evaluated by measuring serum 8-hydroxy-2-deoxyguanosine (8-OHdG) by enzyme-linked immunosorbent assay and strand breaks by the comet assay. Results: We found that TXN was under expressed in both AML and ALL groups (P < 0.001 for both) as compared to the control group. Also TXN expression level was negatively correlated with serum 8-OHdG and tail moment in both AML (P = 0.042 and 0.047, respectively) and ALL (P < 0.001 and P = 0.02, respectively) while it showed no correlation with treatment outcome in either groups. Discussion: This study suggests that TXN expression is hindered in adult acute leukemia which augments oxidative DNA damage and hence mutagenesis. Conclusion: This study provides a new insight into the pathogenesis of acute leukemia and suggests TXN as a new screening test for the risk for acute leukemia.