Increased glutathione in chronic lymphocytic leukemia lymphocytes

Ferraris, Anna Maria; Rolfo, Michela; Mangerini, Rosa; Gaetani, Gian Franco

doi:10.1002/ajh.2830470318

Cited by 35 publications

(16 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Malondialdehyde and 8-oxo-dG levels were significantly increased in gastric tumors in comparison with normal mucosa. Reduced glutathione levels were also increased in cancer tissues, consistent with previous research demonstrating that tripeptide levels were significantly elevated in tumor specimens [16–18] and in the blood cells of cancer patients [33,34]. Increased GSH concentration is a common characteristic of tumor cells; this may be related to the increase in GSH synthetase levels found in some tumor cell lines [35] and is responsible for the reduced sensitivity of cancer cells to chemotherapy and radiotherapy [36].…”

Section: Resultssupporting

confidence: 88%

Oxidative Stress and DNA Damage in Human Gastric Carcinoma: 8-Oxo-7'8-dihydro-2'-deoxyguanosine (8-oxo-dG) as a Possible Tumor Marker

Borrego

Vázquez

Dası́

et al. 2013

IJMS

View full text Add to dashboard Cite

We characterized the oxidative stress (OS) status by the levels of reduced/oxidized glutathione (GSH/GSSG), malondialdehyde (MDA) and the mutagenic base 8-oxo-7′8-dihydro-2′-deoxyguanosine (8-oxo-dG) in human gastric carcinoma (HGC) samples and compared the results with normal tissue from the same patients. We also analyzed 8-oxo-dG in peripheral mononuclear cells (PMNC) and urine from healthy control subjects and in affected patients in the basal state and one, three, six, nine and twelve months after tumor resection. The levels of DNA repair enzyme mRNA expression (hOGG1, RAD51, MUYTH and MTH1) were determined in tumor specimens and compared with normal mucosa. Tumor specimens exhibited increased levels of MDA and 8-oxo-dG compared with normal gastric tissue. GSH levels were also increased, while GSSG levels remained stable. DNA repair enzyme mRNA expression was induced in the tumor tissues. Levels of 8-oxo-dG were significantly elevated in both urine and PMNC of gastric cancer patients compared with healthy controls. After gastrectomy, the levels of the damaged base in urine and PMNC decreased progressively to values close to those found in the healthy population. The high levels of 8-oxo-dG in urine may be related to the increased induction of DNA repair activity in tumor tissue, and the changes observed after tumor resection support its potential use as a tumor marker.

show abstract

Section: Resultssupporting

confidence: 88%

Oxidative Stress and DNA Damage in Human Gastric Carcinoma: 8-Oxo-7'8-dihydro-2'-deoxyguanosine (8-oxo-dG) as a Possible Tumor Marker

Borrego

Vázquez

Dası́

et al. 2013

IJMS

View full text Add to dashboard Cite

show abstract

“…From a study of chronic lymphatic leukemia, there is some evidence for glutathione being higher in leukemic cells compared with lymphocytes. 26 Elevated glutathione levels in tumor tissue compared with the equivalent normal tissue have been reported 27 ; these findings would support the proposal that high glutathione levels are specific to the leukemic cells.…”

Section: Discussionsupporting

confidence: 75%

Raised blast glutathione levels are associated with an increased risk of relapse in childhood acute lymphocytic leukemia

Kearns

Pieters

Rottier

et al. 2001

Blood

View full text Add to dashboard Cite

A preliminary study has linked raised blast glutathione levels with chemoresistance in acute myeloid and lymphoblastic leukemia in adults and children. In this study, therefore, the relationship between leukemic blast glutathione levels and prognosis in childhood acute lymphoblastic leukemia (ALL) was investigated. A total of 77 childhood ALL samples were analyzed, 62 at initial presentation and 15 at relapse. A 20-fold interindividual variation in glutathione levels at presentation (median, 6.54 nmol/mg protein; range, 1.37 to 27.9) was demonstrated. The median level in T-lineage ALL was 2.3-fold higher than in B-lineage ALL (Mann-Whitney test, P < .0001). There was a significant correlation between presenting white cell count (WBC) and glutathione level (Spearman rank correlation coefficient, ‫؍‬ 0.45, P ‫؍‬ .001). A high DNA index correlated with low glutathione levels (MannWhitney test, P ‫؍‬ .013). There was no significant relationship between glutathione levels and in vitro drug sensitivity. Patients with glutathione levels above the median had a significantly greater risk of relapse (log-rank test statistic, 5.55; P ‫؍‬ .018), and the overall survival rate was significantly reduced (logrank test statistic, 4.38; P ‫؍‬ .04). Multivariate analysis demonstrated that glutathione concentration was of independent prognostic value when assessed in conjunction with age, gender, WBC, and immunophenotype. The association of elevated blast glutathione levels with an increased risk of relapse suggests that glutathione-depleting agents may be of therapeutic value in patients who present with a high WBC. (Blood. 2001;97:393-398)

show abstract

“…The levels of GSH in CLL cells are comparable to healthy cells and sometimes even greater 2,29-31 . This could be in part due to the cell's attempt to compensate for its compromised antioxidant enzyme activity.…”

Section: Discussionmentioning

confidence: 81%

Arsenic trioxide and ascorbic acid demonstrate promising activity against primary human CLL cells in vitro

et al. 2010

View full text Add to dashboard Cite

The compromised antioxidant defense system in chronic lymphocytic leukemia (CLL) suggested a potential use for Reactive Oxygen Species (ROS) generating Arsenic Trioxide (ATO) and Ascorbic Acid. While both ATO and ascorbic acid mediated cytotoxicity in CLL B cells as single agents, the efficacy of ATO is enhanced by ascorbic acid. This effect is dependent on increased ROS accumulation, as pretreatment of B-CLL cells with a glutathione reducing buthionine sulfoximine or catalase inhibiting aminotriazole, enhanced ATO/ascorbic acid mediated cytotoxicity. Petreatment with reducing agents such as catalase, or thiol anti-oxidant, N-acetyl cysteine or GSH also abrogated ATO/ascorbic acid mediated cytotoxicity. Furthermore, Hu1D10 mediated cell death was enhanced with ATO and ascorbic acid, thus justifying potential combination of ATO/arsenic trioxide therapy with antibodies such as Hu1D10 that also cause accumulation of ROS.

show abstract

Increased glutathione in chronic lymphocytic leukemia lymphocytes

Cited by 35 publications

References 9 publications

Oxidative Stress and DNA Damage in Human Gastric Carcinoma: 8-Oxo-7'8-dihydro-2'-deoxyguanosine (8-oxo-dG) as a Possible Tumor Marker

Oxidative Stress and DNA Damage in Human Gastric Carcinoma: 8-Oxo-7'8-dihydro-2'-deoxyguanosine (8-oxo-dG) as a Possible Tumor Marker

Raised blast glutathione levels are associated with an increased risk of relapse in childhood acute lymphocytic leukemia

Arsenic trioxide and ascorbic acid demonstrate promising activity against primary human CLL cells in vitro

Contact Info

Product

Resources

About