Contributions
Abstract: PB1763
Type: Publication Only
Background
Chronic lymphocytic leukemia (CLL) is the most prevalent leukemia in the western adult population. Although advanced age, white ancestry, and family history of hematologic malignancies are risk factors, the etiology of CLL still unknown. One of the mechanisms associated with the development of this pathology is related to the oxidative stress (OS) resulting from an imbalance between the production of reactive oxygen species (ROS) and their disposal by the antioxidant defenses. The nuclear factor erythroid 2-like gene - type 2 (NFE2L2) and its suppressor, the Kelch-like ECH-associated protein 1 (KEAP1) gene, plays a central role in ROS balance. Changes in these genes, whether due to somatic mutations or genetic variants (SNPs), have been associated with some hematological diseases. However, the role of NFE2L2 and KEAP1 genes polymorphisms in susceptibility and prognosis of CLL is not studied.
Aims
To assess the role of two SNPs in the NFE2L2 and KEAP1 genes on CLL susceptibility, their influence on prognosis/survival, and their correlation with clinical and laboratory characteristics of patients.
Methods
Genetic variants rs13001694 (NFE2L2) and rs11085735 (KEAP1) were genotyped by tetra-primers-AMRS-PCR in 176 patients with CLL and 261 controls. The role of these genes polymorphisms in CLL susceptibility and their association with clinical and laboratory characteristics as well as with therapy response was assessed by logistic regression analysis and/or by Fisher's exact test. The influence on prognosis and survival was performed through Kaplan-Meier curves by estimating the progression free survival (PFS) and the overall survival (OS).
Results
The results showed that individuals with the GG genotype (NFE2L2) are at higher risk of developing CLL [Odds ratio (OR): 2.032; 95% confidence interval (CI): 1,234-3,351; P = 0.004]. In addition, the genotypic profile (GP) GG / CC (NFE2L2 / KEAP1) is a risk factor (OR: 2.186; 95% CI: 1.279-3.744; p = 0.003) for the development of CLL while the AA / CC profile constitutes a protective factor (OR: 0.634, 95% CI: 0.407-0.984, p = 0.037). In contrast, patients with genotype AG (NFE2L2) and/or CC (KEAP1) had a higher rate of complete response to rituximab therapy regimens (NFE2L2 AG: OR 1.6, 95% CI 1.063-3.933, p = 0.037; KEAP1 CC, OR 1.2, 95% CI 1.041-3.477, p = 0.045, NFE2L2 / KEAP1 AG / CC: OR 1.9, 95% CI, 1.843-4.485, p = 0.017) and with fludarabine (NFE2L2 / KEAP1 AG / CC: OR 1.5, 95% CI, 1.119-3.887, p = 0.026). Finally, the overall survival of CLL patients appears to be influenced by the genotypic profile of NFE2L2 / KEAP1 [GP AG / AC patients have a lower mean survival (72.5 ± 13.8 months) than patients with other GPs (139.4 ± 10.2 months, p = 0.037)], while progression-free survival seems to be influenced by the KEAP1 genotype [patients with CC genotype have a longer mean survival (198.0 ± 13.6 months) than patients with AA and AC genotypes (85.3 ± 13.4 months; P = 0.022)].
Conclusion
Session topic: 5. Chronic lymphocytic leukemia and related disorders - Biology
Keyword(s): Rituximab, Prognostic factor, Leukemia, Fludarabine
Abstract: PB1763
Type: Publication Only
Background
Chronic lymphocytic leukemia (CLL) is the most prevalent leukemia in the western adult population. Although advanced age, white ancestry, and family history of hematologic malignancies are risk factors, the etiology of CLL still unknown. One of the mechanisms associated with the development of this pathology is related to the oxidative stress (OS) resulting from an imbalance between the production of reactive oxygen species (ROS) and their disposal by the antioxidant defenses. The nuclear factor erythroid 2-like gene - type 2 (NFE2L2) and its suppressor, the Kelch-like ECH-associated protein 1 (KEAP1) gene, plays a central role in ROS balance. Changes in these genes, whether due to somatic mutations or genetic variants (SNPs), have been associated with some hematological diseases. However, the role of NFE2L2 and KEAP1 genes polymorphisms in susceptibility and prognosis of CLL is not studied.
Aims
To assess the role of two SNPs in the NFE2L2 and KEAP1 genes on CLL susceptibility, their influence on prognosis/survival, and their correlation with clinical and laboratory characteristics of patients.
Methods
Genetic variants rs13001694 (NFE2L2) and rs11085735 (KEAP1) were genotyped by tetra-primers-AMRS-PCR in 176 patients with CLL and 261 controls. The role of these genes polymorphisms in CLL susceptibility and their association with clinical and laboratory characteristics as well as with therapy response was assessed by logistic regression analysis and/or by Fisher's exact test. The influence on prognosis and survival was performed through Kaplan-Meier curves by estimating the progression free survival (PFS) and the overall survival (OS).
Results
The results showed that individuals with the GG genotype (NFE2L2) are at higher risk of developing CLL [Odds ratio (OR): 2.032; 95% confidence interval (CI): 1,234-3,351; P = 0.004]. In addition, the genotypic profile (GP) GG / CC (NFE2L2 / KEAP1) is a risk factor (OR: 2.186; 95% CI: 1.279-3.744; p = 0.003) for the development of CLL while the AA / CC profile constitutes a protective factor (OR: 0.634, 95% CI: 0.407-0.984, p = 0.037). In contrast, patients with genotype AG (NFE2L2) and/or CC (KEAP1) had a higher rate of complete response to rituximab therapy regimens (NFE2L2 AG: OR 1.6, 95% CI 1.063-3.933, p = 0.037; KEAP1 CC, OR 1.2, 95% CI 1.041-3.477, p = 0.045, NFE2L2 / KEAP1 AG / CC: OR 1.9, 95% CI, 1.843-4.485, p = 0.017) and with fludarabine (NFE2L2 / KEAP1 AG / CC: OR 1.5, 95% CI, 1.119-3.887, p = 0.026). Finally, the overall survival of CLL patients appears to be influenced by the genotypic profile of NFE2L2 / KEAP1 [GP AG / AC patients have a lower mean survival (72.5 ± 13.8 months) than patients with other GPs (139.4 ± 10.2 months, p = 0.037)], while progression-free survival seems to be influenced by the KEAP1 genotype [patients with CC genotype have a longer mean survival (198.0 ± 13.6 months) than patients with AA and AC genotypes (85.3 ± 13.4 months; P = 0.022)].
Conclusion
Session topic: 5. Chronic lymphocytic leukemia and related disorders - Biology
Keyword(s): Rituximab, Prognostic factor, Leukemia, Fludarabine