Contributions
Abstract: PB1771
Type: Publication Only
Background
Human concentrative nucleoside transporter 3 (hCNT3) belongs to a family of nucleoside transporters involved in fludarabine cellular uptake. It has been reportedthat overexpression of SLC28A3 gene encoding hCNT3 predictspoor response to fludarabin-based chemotherapy.However, the mechanisms by which elevated expression of SLC28A3 mediate fludarabine resistance are still elusive.
Aims
The aim of the study was to examine possible influence of SLC28A3 gene overexpression on treatment response to fludarabine-cyclophosphamide therapy (FC) in patients with chronic lymohocytic leukemia.
Methods
We retrospectively analysed data from 54 CLL patients diagnosed and treated at Clinic for Hematology, Clinical Center of Serbia from 2003 to 2013. Blood samples were prospectively collected and analysed for biological and molecular features, as well as standard laboratory parameters. The expression of SLC28A3 gene was analyzed in peripheral blood mononuclear cells by RQ-PCR methodology, using TaqMan chemistry and Abl as endogenous control gene. Quantification of target gene expression was made by comparative ddCt method, using HL-60 cell line as the calibrator. All analyses were done prior to any treatment.
Results
Median age at diagnosis was 57 years (range 38-75). All patients were treated with fludarabin-based chemotherapy, 45 (83%) in the first treatment line. Overall response rate to the first line therapy was 81%, equally distributed on complete and partial responses (CR and PR), while the remainder included the same number of patients with stable disease (SD) and progressive disease (PD) (5, 9.6%). Most of the patients (42, 78%) relapsed during the follow up. At the time of the last follow up 14 (26%) patients were still alive, 35 (65%) were dead, and 5 (9%) were lost to follow up. Median overal survival was 76 months.
Conclusion
Overexpression of SLC28A3 gene is a predictor of resistance to treatment with FC chemotherapy. Further studies are warranted to confirm these findings.
Session topic: 5. Chronic lymphocytic leukemia and related disorders - Biology
Keyword(s): Overexpression, Fludarabine, Resistance
Abstract: PB1771
Type: Publication Only
Background
Human concentrative nucleoside transporter 3 (hCNT3) belongs to a family of nucleoside transporters involved in fludarabine cellular uptake. It has been reportedthat overexpression of SLC28A3 gene encoding hCNT3 predictspoor response to fludarabin-based chemotherapy.However, the mechanisms by which elevated expression of SLC28A3 mediate fludarabine resistance are still elusive.
Aims
The aim of the study was to examine possible influence of SLC28A3 gene overexpression on treatment response to fludarabine-cyclophosphamide therapy (FC) in patients with chronic lymohocytic leukemia.
Methods
We retrospectively analysed data from 54 CLL patients diagnosed and treated at Clinic for Hematology, Clinical Center of Serbia from 2003 to 2013. Blood samples were prospectively collected and analysed for biological and molecular features, as well as standard laboratory parameters. The expression of SLC28A3 gene was analyzed in peripheral blood mononuclear cells by RQ-PCR methodology, using TaqMan chemistry and Abl as endogenous control gene. Quantification of target gene expression was made by comparative ddCt method, using HL-60 cell line as the calibrator. All analyses were done prior to any treatment.
Results
Median age at diagnosis was 57 years (range 38-75). All patients were treated with fludarabin-based chemotherapy, 45 (83%) in the first treatment line. Overall response rate to the first line therapy was 81%, equally distributed on complete and partial responses (CR and PR), while the remainder included the same number of patients with stable disease (SD) and progressive disease (PD) (5, 9.6%). Most of the patients (42, 78%) relapsed during the follow up. At the time of the last follow up 14 (26%) patients were still alive, 35 (65%) were dead, and 5 (9%) were lost to follow up. Median overal survival was 76 months.
Conclusion
Overexpression of SLC28A3 gene is a predictor of resistance to treatment with FC chemotherapy. Further studies are warranted to confirm these findings.
Session topic: 5. Chronic lymphocytic leukemia and related disorders - Biology
Keyword(s): Overexpression, Fludarabine, Resistance