Contributions
Abstract: PB1964
Type: Publication Only
Background
Chronic myeloid leukemia (CML) is a chronic myeloproliferative neoplasm arising from the reciprocal translocation t(9;22) which is the source for the bcr-abl P210 protein that determines the development and perpetuation of the leukemic granulocytic clone. Increased levels of oxidative stress, defined as an imbalance of the redox status of the cell induced by overproduction of reactive oxygen species or decreased antioxidant defense, lead to chromosomal abnormalities, promote genomic instability and blastic transformation, and are possibly responsible for the development of resistance to tyrosin-kinase inhibitors (TKI). The involvement of oxidative stress has been studied in aging and other physiological processes, and also in a couple of hematological disorders: essential thrombocythemia, chronic lymphocytic leukemia or primary immune thrombocytopenia1-8.
Aims
To evaluate the levels of oxidative stress and the total antioxidant capacity in order to establish a possible link between oxidative stress, TKI therapy and molecular response in patients with CML.
Methods
We evaluated 26 patients with chronic phase CML, diagnosed according to the ELN/WHO criteria, hospitalised in the Clinic of Hematology, Filantropia City Hospital Craiova, Romania, compared to healthy controls. Informed consent was obtained from all recruited participants. The patients were treated with first or second generation TKI. Oxidative stress was evaluated at diagnosis and when switching from first to second generation of TKI was decided, and correlated with the molecular response (MR). We evaluated the total antioxidant capacity (TAC) using a multidetection microplate reader FLUOstar Omega and a Sigma-Aldrich antioxidant assay kit. The BCR-ABL transcript was detected by RT-PCR. The statistical analysis was performed using the student T-test and a p-value ≤ 0.05 was considered significant.
Results
The study group included 14 males and 12 females (age range 23-84 years). The patients were treated with first generation TKI as first line therapy. Due to intolerance or failure to first generation TKI, 7 patients required second generation TKI as second line therapy. All patients with CML had low levels of TAC compared to healthy controls (p≤ 0.05), with a lower level in patients with intolerance or failure to first generation TKI and switched to second generation TKI (p≤ 0.05). We found a significant correlation between the low level of TAC, types of TKI, BCR-ABL transcript and MR.
Conclusion
In our study group, low levels of TAC were found in CML patients compared to healthy controls. Patients that were switched from first to second generation of TKI had significantly lower TAC levels. Our study is ongoing, but we suppose that oxidative stress plays a role in genomic instability and self-mutagenesis, causing TKI resistance via a bcr-abl independent mechanism.
References: 1. Gaman MA, et al. Haematologica. 2017; 102(s2):835. abstract n. PB2105.
2. Gaman AM, et al. Rom J Morphol Embryol. 2013;54(4):1141-5.
3. Gaman AM, et al. Aging Dis. 2016 May 27;7(3):307-17. doi: 10.14336/AD.2015.1022.
4. Gaman AM, et al. Oxid Med Cell Longev. 2014;2014:158135. doi: 10.1155/2014/158135.
5. Gaman AM, et al. Haematologica. 2014; 99(s1):773. abstract n. PB2030. 6. Gaman MA, et al. Haematologica. 2017; 102(s2):840. abstract n. PB2119. 7. Gaman AM, et al. Haematologica. 2015; 100(s1):772. abstract n. PB1967. 8. Crisan AM, et al. Rom J Morphol Embryol. 2015;56(3):1145-51.
Session topic: 8. Chronic myeloid leukemia - Clinical
Keyword(s): Antioxidants, Molecular response, Philadelphia chromosome, Reactive oxygen species
Abstract: PB1964
Type: Publication Only
Background
Chronic myeloid leukemia (CML) is a chronic myeloproliferative neoplasm arising from the reciprocal translocation t(9;22) which is the source for the bcr-abl P210 protein that determines the development and perpetuation of the leukemic granulocytic clone. Increased levels of oxidative stress, defined as an imbalance of the redox status of the cell induced by overproduction of reactive oxygen species or decreased antioxidant defense, lead to chromosomal abnormalities, promote genomic instability and blastic transformation, and are possibly responsible for the development of resistance to tyrosin-kinase inhibitors (TKI). The involvement of oxidative stress has been studied in aging and other physiological processes, and also in a couple of hematological disorders: essential thrombocythemia, chronic lymphocytic leukemia or primary immune thrombocytopenia1-8.
Aims
To evaluate the levels of oxidative stress and the total antioxidant capacity in order to establish a possible link between oxidative stress, TKI therapy and molecular response in patients with CML.
Methods
We evaluated 26 patients with chronic phase CML, diagnosed according to the ELN/WHO criteria, hospitalised in the Clinic of Hematology, Filantropia City Hospital Craiova, Romania, compared to healthy controls. Informed consent was obtained from all recruited participants. The patients were treated with first or second generation TKI. Oxidative stress was evaluated at diagnosis and when switching from first to second generation of TKI was decided, and correlated with the molecular response (MR). We evaluated the total antioxidant capacity (TAC) using a multidetection microplate reader FLUOstar Omega and a Sigma-Aldrich antioxidant assay kit. The BCR-ABL transcript was detected by RT-PCR. The statistical analysis was performed using the student T-test and a p-value ≤ 0.05 was considered significant.
Results
The study group included 14 males and 12 females (age range 23-84 years). The patients were treated with first generation TKI as first line therapy. Due to intolerance or failure to first generation TKI, 7 patients required second generation TKI as second line therapy. All patients with CML had low levels of TAC compared to healthy controls (p≤ 0.05), with a lower level in patients with intolerance or failure to first generation TKI and switched to second generation TKI (p≤ 0.05). We found a significant correlation between the low level of TAC, types of TKI, BCR-ABL transcript and MR.
Conclusion
In our study group, low levels of TAC were found in CML patients compared to healthy controls. Patients that were switched from first to second generation of TKI had significantly lower TAC levels. Our study is ongoing, but we suppose that oxidative stress plays a role in genomic instability and self-mutagenesis, causing TKI resistance via a bcr-abl independent mechanism.
References: 1. Gaman MA, et al. Haematologica. 2017; 102(s2):835. abstract n. PB2105.
2. Gaman AM, et al. Rom J Morphol Embryol. 2013;54(4):1141-5.
3. Gaman AM, et al. Aging Dis. 2016 May 27;7(3):307-17. doi: 10.14336/AD.2015.1022.
4. Gaman AM, et al. Oxid Med Cell Longev. 2014;2014:158135. doi: 10.1155/2014/158135.
5. Gaman AM, et al. Haematologica. 2014; 99(s1):773. abstract n. PB2030. 6. Gaman MA, et al. Haematologica. 2017; 102(s2):840. abstract n. PB2119. 7. Gaman AM, et al. Haematologica. 2015; 100(s1):772. abstract n. PB1967. 8. Crisan AM, et al. Rom J Morphol Embryol. 2015;56(3):1145-51.
Session topic: 8. Chronic myeloid leukemia - Clinical
Keyword(s): Antioxidants, Molecular response, Philadelphia chromosome, Reactive oxygen species