OXIDATIVE STRESS IN CHRONIC LYMPHOCYTIC LEUKEMIA
(Abstract release date: 05/19/16)
EHA Library. D'Arena G. 06/09/16; 134670; PB1770
Dr. Giovanni D'Arena
Contributions
Contributions
Abstract
Abstract: PB1770
Type: Publication Only
Background
Oxidative stress (OS) is an imbalance between production of free radicals and reactive metabolites, so-called oxidants or reactive oxygen species (ROS), and their elimination by protective mechanisms, referred to as antioxidants. Extensive evidence has shown that disturbances of oxidative metabolism are a common feature of transformed tumor cells. However, the effect of OS levels in chronic lymphocytic leukemia (CLL) is largely unknown.
Aims
To investigate the oxidative stress status in CLL and analyze the relationship with the disease status and prognostic factors evaluated at diagnosis.
Methods
We analyzed peripheral blood samples from 76 patients with untreated CLL evaluated at diagnosis (48 male and 28 female; mean age 67 years; range 36-90 years; 57 patients with A Binet stage, 15 patients with B stage, and 4 patients with C stage) and 20 healthy individuals as matched control group. Serum total antioxidant capacity was determined by performing the d-ROMs test, whose chemical principle is based on the ability of a biological sample to oxidize N,N-diethylparaphenilenediamine (normal range 250-300 U CARR, where 1 U CARR is equivalent to 0.8 mg/L H2O2), while serum OS was assessed by means of BAP test, which measures the ability of a serum sample to reduce iron from the ferric to the ferrous ionic form (optimal value >2.200 micromol/L reduced iron).
Results
A significant oxidative damage was showed in CLL patients (d-ROMs test: 407 U CARR ± 194; range 194 - 794; BAP-test: 2.033 micromol/L ± 310.6; range 1.024 – 3.300) with respect to normal controls (d-ROMs test: 259.6 U CARR ± 87.5; range 158 - 425; BAP-test: 2.505 micromol/L ± 306; range 1.876-3.045) (p 0.0014 and 0.0001, respectively). However, no correlations were found with absolute lymphocytosis, haemoglobin and platelet levels, Binet disease stage and cytogenetics abnormalities (evaluated only in 52 patients) detected by FISH (normal vs del17p vs del11q vs trisomy12 vs del13q14). Unmutated IgVH CLL patients displayed significantly higher d-ROMs test values than mutated IgVH patients (p 0.0057). On the contrary, no differences were found in BAP test according to mutational IgVH status. At a mean follow-up of 50 months (range 6-211 months), 16 patients progressed needing treatment. d-ROMS test was found significantly higher at diagnosis in this cohort of patients with respect to non progressed patients (501 U CARR ± 135 vs 385 ± 149; p 0.006). No differences were also found with respect to BAP test. Finally, no correlations were found between time to treatment and both d-ROMS and BAP test levels.
Conclusion
CLL patients show oxidative stress features (increased oxidative damage, evaluated by d-ROMs test, and reduced antioxidant capacity, measured by means of BAP test) which are usually irrespective of clinical and biological characteristics detected at diagnosis, reflecting constitutive CLL findings, rather than disease burden and activity. In particular, differently from a previous observation (Collado R et al, 2014), no correlations were found in our cohort of patients between increased oxidative damage and unfavourable cytogenetics subgroups. Our data support the investigational use of antioxidants in the clinical setting.
Session topic: E-poster
Keyword(s): Chronic lymphocytic leukemia, Prognostic factor
Type: Publication Only
Background
Oxidative stress (OS) is an imbalance between production of free radicals and reactive metabolites, so-called oxidants or reactive oxygen species (ROS), and their elimination by protective mechanisms, referred to as antioxidants. Extensive evidence has shown that disturbances of oxidative metabolism are a common feature of transformed tumor cells. However, the effect of OS levels in chronic lymphocytic leukemia (CLL) is largely unknown.
Aims
To investigate the oxidative stress status in CLL and analyze the relationship with the disease status and prognostic factors evaluated at diagnosis.
Methods
We analyzed peripheral blood samples from 76 patients with untreated CLL evaluated at diagnosis (48 male and 28 female; mean age 67 years; range 36-90 years; 57 patients with A Binet stage, 15 patients with B stage, and 4 patients with C stage) and 20 healthy individuals as matched control group. Serum total antioxidant capacity was determined by performing the d-ROMs test, whose chemical principle is based on the ability of a biological sample to oxidize N,N-diethylparaphenilenediamine (normal range 250-300 U CARR, where 1 U CARR is equivalent to 0.8 mg/L H2O2), while serum OS was assessed by means of BAP test, which measures the ability of a serum sample to reduce iron from the ferric to the ferrous ionic form (optimal value >2.200 micromol/L reduced iron).
Results
A significant oxidative damage was showed in CLL patients (d-ROMs test: 407 U CARR ± 194; range 194 - 794; BAP-test: 2.033 micromol/L ± 310.6; range 1.024 – 3.300) with respect to normal controls (d-ROMs test: 259.6 U CARR ± 87.5; range 158 - 425; BAP-test: 2.505 micromol/L ± 306; range 1.876-3.045) (p 0.0014 and 0.0001, respectively). However, no correlations were found with absolute lymphocytosis, haemoglobin and platelet levels, Binet disease stage and cytogenetics abnormalities (evaluated only in 52 patients) detected by FISH (normal vs del17p vs del11q vs trisomy12 vs del13q14). Unmutated IgVH CLL patients displayed significantly higher d-ROMs test values than mutated IgVH patients (p 0.0057). On the contrary, no differences were found in BAP test according to mutational IgVH status. At a mean follow-up of 50 months (range 6-211 months), 16 patients progressed needing treatment. d-ROMS test was found significantly higher at diagnosis in this cohort of patients with respect to non progressed patients (501 U CARR ± 135 vs 385 ± 149; p 0.006). No differences were also found with respect to BAP test. Finally, no correlations were found between time to treatment and both d-ROMS and BAP test levels.
Conclusion
CLL patients show oxidative stress features (increased oxidative damage, evaluated by d-ROMs test, and reduced antioxidant capacity, measured by means of BAP test) which are usually irrespective of clinical and biological characteristics detected at diagnosis, reflecting constitutive CLL findings, rather than disease burden and activity. In particular, differently from a previous observation (Collado R et al, 2014), no correlations were found in our cohort of patients between increased oxidative damage and unfavourable cytogenetics subgroups. Our data support the investigational use of antioxidants in the clinical setting.
Session topic: E-poster
Keyword(s): Chronic lymphocytic leukemia, Prognostic factor
Abstract: PB1770
Type: Publication Only
Background
Oxidative stress (OS) is an imbalance between production of free radicals and reactive metabolites, so-called oxidants or reactive oxygen species (ROS), and their elimination by protective mechanisms, referred to as antioxidants. Extensive evidence has shown that disturbances of oxidative metabolism are a common feature of transformed tumor cells. However, the effect of OS levels in chronic lymphocytic leukemia (CLL) is largely unknown.
Aims
To investigate the oxidative stress status in CLL and analyze the relationship with the disease status and prognostic factors evaluated at diagnosis.
Methods
We analyzed peripheral blood samples from 76 patients with untreated CLL evaluated at diagnosis (48 male and 28 female; mean age 67 years; range 36-90 years; 57 patients with A Binet stage, 15 patients with B stage, and 4 patients with C stage) and 20 healthy individuals as matched control group. Serum total antioxidant capacity was determined by performing the d-ROMs test, whose chemical principle is based on the ability of a biological sample to oxidize N,N-diethylparaphenilenediamine (normal range 250-300 U CARR, where 1 U CARR is equivalent to 0.8 mg/L H2O2), while serum OS was assessed by means of BAP test, which measures the ability of a serum sample to reduce iron from the ferric to the ferrous ionic form (optimal value >2.200 micromol/L reduced iron).
Results
A significant oxidative damage was showed in CLL patients (d-ROMs test: 407 U CARR ± 194; range 194 - 794; BAP-test: 2.033 micromol/L ± 310.6; range 1.024 – 3.300) with respect to normal controls (d-ROMs test: 259.6 U CARR ± 87.5; range 158 - 425; BAP-test: 2.505 micromol/L ± 306; range 1.876-3.045) (p 0.0014 and 0.0001, respectively). However, no correlations were found with absolute lymphocytosis, haemoglobin and platelet levels, Binet disease stage and cytogenetics abnormalities (evaluated only in 52 patients) detected by FISH (normal vs del17p vs del11q vs trisomy12 vs del13q14). Unmutated IgVH CLL patients displayed significantly higher d-ROMs test values than mutated IgVH patients (p 0.0057). On the contrary, no differences were found in BAP test according to mutational IgVH status. At a mean follow-up of 50 months (range 6-211 months), 16 patients progressed needing treatment. d-ROMS test was found significantly higher at diagnosis in this cohort of patients with respect to non progressed patients (501 U CARR ± 135 vs 385 ± 149; p 0.006). No differences were also found with respect to BAP test. Finally, no correlations were found between time to treatment and both d-ROMS and BAP test levels.
Conclusion
CLL patients show oxidative stress features (increased oxidative damage, evaluated by d-ROMs test, and reduced antioxidant capacity, measured by means of BAP test) which are usually irrespective of clinical and biological characteristics detected at diagnosis, reflecting constitutive CLL findings, rather than disease burden and activity. In particular, differently from a previous observation (Collado R et al, 2014), no correlations were found in our cohort of patients between increased oxidative damage and unfavourable cytogenetics subgroups. Our data support the investigational use of antioxidants in the clinical setting.
Session topic: E-poster
Keyword(s): Chronic lymphocytic leukemia, Prognostic factor
Type: Publication Only
Background
Oxidative stress (OS) is an imbalance between production of free radicals and reactive metabolites, so-called oxidants or reactive oxygen species (ROS), and their elimination by protective mechanisms, referred to as antioxidants. Extensive evidence has shown that disturbances of oxidative metabolism are a common feature of transformed tumor cells. However, the effect of OS levels in chronic lymphocytic leukemia (CLL) is largely unknown.
Aims
To investigate the oxidative stress status in CLL and analyze the relationship with the disease status and prognostic factors evaluated at diagnosis.
Methods
We analyzed peripheral blood samples from 76 patients with untreated CLL evaluated at diagnosis (48 male and 28 female; mean age 67 years; range 36-90 years; 57 patients with A Binet stage, 15 patients with B stage, and 4 patients with C stage) and 20 healthy individuals as matched control group. Serum total antioxidant capacity was determined by performing the d-ROMs test, whose chemical principle is based on the ability of a biological sample to oxidize N,N-diethylparaphenilenediamine (normal range 250-300 U CARR, where 1 U CARR is equivalent to 0.8 mg/L H2O2), while serum OS was assessed by means of BAP test, which measures the ability of a serum sample to reduce iron from the ferric to the ferrous ionic form (optimal value >2.200 micromol/L reduced iron).
Results
A significant oxidative damage was showed in CLL patients (d-ROMs test: 407 U CARR ± 194; range 194 - 794; BAP-test: 2.033 micromol/L ± 310.6; range 1.024 – 3.300) with respect to normal controls (d-ROMs test: 259.6 U CARR ± 87.5; range 158 - 425; BAP-test: 2.505 micromol/L ± 306; range 1.876-3.045) (p 0.0014 and 0.0001, respectively). However, no correlations were found with absolute lymphocytosis, haemoglobin and platelet levels, Binet disease stage and cytogenetics abnormalities (evaluated only in 52 patients) detected by FISH (normal vs del17p vs del11q vs trisomy12 vs del13q14). Unmutated IgVH CLL patients displayed significantly higher d-ROMs test values than mutated IgVH patients (p 0.0057). On the contrary, no differences were found in BAP test according to mutational IgVH status. At a mean follow-up of 50 months (range 6-211 months), 16 patients progressed needing treatment. d-ROMS test was found significantly higher at diagnosis in this cohort of patients with respect to non progressed patients (501 U CARR ± 135 vs 385 ± 149; p 0.006). No differences were also found with respect to BAP test. Finally, no correlations were found between time to treatment and both d-ROMS and BAP test levels.
Conclusion
CLL patients show oxidative stress features (increased oxidative damage, evaluated by d-ROMs test, and reduced antioxidant capacity, measured by means of BAP test) which are usually irrespective of clinical and biological characteristics detected at diagnosis, reflecting constitutive CLL findings, rather than disease burden and activity. In particular, differently from a previous observation (Collado R et al, 2014), no correlations were found in our cohort of patients between increased oxidative damage and unfavourable cytogenetics subgroups. Our data support the investigational use of antioxidants in the clinical setting.
Session topic: E-poster
Keyword(s): Chronic lymphocytic leukemia, Prognostic factor
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