THE EXPRESSION OF TOLL-LIKE RECEPTORS IN PATIENTS WITH B-CELL CHRONIC LYMPHOCYTIC LEUKEMIA.
(Abstract release date: 05/19/16)
EHA Library. Rybka J. 06/09/16; 134673; PB1773
Dr. Justyna Rybka
Contributions
Contributions
Abstract
Abstract: PB1773
Type: Publication Only
Background
B-cell chronic lymphocytic leukemia (B-CLL) presents with progressive accumulation of monoclonal B-cells in the peripheral blood, bone marrow and lymphoid organs. B-CLL is characterized by heterogenous clinical outcome. Some patients have an indolent disease and the others have an aggressive clinical course of B-CLL. Toll-like receptors (TLRs) play an important role in B-cell activation and maturation and may be involved in the pathogenesis of B-cell lymphomas. TLRs are essential receptors of the innate immune system and key regulators of the acquired immune system. TLRs are mainly expressed in human immune related cells such as monocytes, neutrophils, macrophages, dendritic cells, T cells, B cells and NK cells. The expression of TLRs and their association with other prognostic factors in B-CLL patients remains unclear.
Aims
The aim of our study was to evaluate the expression of TLR2, TLR4 and TLR9 and their significance as biological markers in patients with B-cell chronic lymphocytic leukemia.
Methods
60 patients with newly diagnosed B-CLL were evaluated (29 females and 31 males). The median age of patients was 68 years (range: 52-88 years). The diagnosis was performed according to the IWCLL/NCI criteria for CLL. 40 patients (67%) had early-stage CLL (Rai stage 0-II) and 20 patients (33%) had advanced-stage CLL (Rai stage III and IV). All patients were either untreated. The healthy control group included 14 age-matched individuals (7 females and 7 males).Using quantitative reverse transcriptase PCR, the mRNA expression of genes TLR2, TLR4 and TLR9 was measured. The relative quantitation was indicated by cycle threshold (Ct) values. The Ct value of the target genes was normalized (ΔCt) to the Ct value of the GUS gene of the samples.The results were statistically analysed using ‘STATISTICA 8,0’. Statistical analysis was performed by means of Mann-Whitney’s U-test and p<0,05 indicated a significant difference. Overall survival (OS) was determined using Kaplan-Meier method. The long-rank test was used to compare the curves.
Results
In comparison to control group TLR2 and TLR4 mRNA expression was higher in B-CLL patients than in healthy individuals (ΔCt TLR2 6.46±9.58 vs 0.98±0.43 and ΔCt TLR4 11.91±70.22 vs 2.21±0.32)(p<0.05). TLR9 mRNA expression was higher in control group than in patients with B-CLL (ΔCt TLR9 23.65±16.29 vs 3.35±1.93)(p<0.05). We found that patients with higher mRNA expression of TLR9 had significantly longer OS than patients with lower mRNA expression of TLR9 (p<0.05).TLR2 mRNA expression was higher in patients with advanced-stage CLL (Rai stages III and IV) than in patients with early-stage disease (Rai stages 0-II) (ΔCt TLR2 19.10±17.76 vs 7.94±6.25) (p<0.05). Moreover we observed that expression of TLR2 in patients with anemia was significant higher than in patients without anemia (ΔCt TLR2 17.18±14.29 vs 7.10±5.98) (p<0.05).
Conclusion
In conclusion, our results suggest that TLRs could become new potential biological markers for the clinical outcome in patients with B-cell chronic lymphocytic leukemia. However, this observation should be validated by a larger study.
Session topic: E-poster
Keyword(s): B cell, Chronic lymphocytic leukemia
Type: Publication Only
Background
B-cell chronic lymphocytic leukemia (B-CLL) presents with progressive accumulation of monoclonal B-cells in the peripheral blood, bone marrow and lymphoid organs. B-CLL is characterized by heterogenous clinical outcome. Some patients have an indolent disease and the others have an aggressive clinical course of B-CLL. Toll-like receptors (TLRs) play an important role in B-cell activation and maturation and may be involved in the pathogenesis of B-cell lymphomas. TLRs are essential receptors of the innate immune system and key regulators of the acquired immune system. TLRs are mainly expressed in human immune related cells such as monocytes, neutrophils, macrophages, dendritic cells, T cells, B cells and NK cells. The expression of TLRs and their association with other prognostic factors in B-CLL patients remains unclear.
Aims
The aim of our study was to evaluate the expression of TLR2, TLR4 and TLR9 and their significance as biological markers in patients with B-cell chronic lymphocytic leukemia.
Methods
60 patients with newly diagnosed B-CLL were evaluated (29 females and 31 males). The median age of patients was 68 years (range: 52-88 years). The diagnosis was performed according to the IWCLL/NCI criteria for CLL. 40 patients (67%) had early-stage CLL (Rai stage 0-II) and 20 patients (33%) had advanced-stage CLL (Rai stage III and IV). All patients were either untreated. The healthy control group included 14 age-matched individuals (7 females and 7 males).Using quantitative reverse transcriptase PCR, the mRNA expression of genes TLR2, TLR4 and TLR9 was measured. The relative quantitation was indicated by cycle threshold (Ct) values. The Ct value of the target genes was normalized (ΔCt) to the Ct value of the GUS gene of the samples.The results were statistically analysed using ‘STATISTICA 8,0’. Statistical analysis was performed by means of Mann-Whitney’s U-test and p<0,05 indicated a significant difference. Overall survival (OS) was determined using Kaplan-Meier method. The long-rank test was used to compare the curves.
Results
In comparison to control group TLR2 and TLR4 mRNA expression was higher in B-CLL patients than in healthy individuals (ΔCt TLR2 6.46±9.58 vs 0.98±0.43 and ΔCt TLR4 11.91±70.22 vs 2.21±0.32)(p<0.05). TLR9 mRNA expression was higher in control group than in patients with B-CLL (ΔCt TLR9 23.65±16.29 vs 3.35±1.93)(p<0.05). We found that patients with higher mRNA expression of TLR9 had significantly longer OS than patients with lower mRNA expression of TLR9 (p<0.05).TLR2 mRNA expression was higher in patients with advanced-stage CLL (Rai stages III and IV) than in patients with early-stage disease (Rai stages 0-II) (ΔCt TLR2 19.10±17.76 vs 7.94±6.25) (p<0.05). Moreover we observed that expression of TLR2 in patients with anemia was significant higher than in patients without anemia (ΔCt TLR2 17.18±14.29 vs 7.10±5.98) (p<0.05).
Conclusion
In conclusion, our results suggest that TLRs could become new potential biological markers for the clinical outcome in patients with B-cell chronic lymphocytic leukemia. However, this observation should be validated by a larger study.
Session topic: E-poster
Keyword(s): B cell, Chronic lymphocytic leukemia
Abstract: PB1773
Type: Publication Only
Background
B-cell chronic lymphocytic leukemia (B-CLL) presents with progressive accumulation of monoclonal B-cells in the peripheral blood, bone marrow and lymphoid organs. B-CLL is characterized by heterogenous clinical outcome. Some patients have an indolent disease and the others have an aggressive clinical course of B-CLL. Toll-like receptors (TLRs) play an important role in B-cell activation and maturation and may be involved in the pathogenesis of B-cell lymphomas. TLRs are essential receptors of the innate immune system and key regulators of the acquired immune system. TLRs are mainly expressed in human immune related cells such as monocytes, neutrophils, macrophages, dendritic cells, T cells, B cells and NK cells. The expression of TLRs and their association with other prognostic factors in B-CLL patients remains unclear.
Aims
The aim of our study was to evaluate the expression of TLR2, TLR4 and TLR9 and their significance as biological markers in patients with B-cell chronic lymphocytic leukemia.
Methods
60 patients with newly diagnosed B-CLL were evaluated (29 females and 31 males). The median age of patients was 68 years (range: 52-88 years). The diagnosis was performed according to the IWCLL/NCI criteria for CLL. 40 patients (67%) had early-stage CLL (Rai stage 0-II) and 20 patients (33%) had advanced-stage CLL (Rai stage III and IV). All patients were either untreated. The healthy control group included 14 age-matched individuals (7 females and 7 males).Using quantitative reverse transcriptase PCR, the mRNA expression of genes TLR2, TLR4 and TLR9 was measured. The relative quantitation was indicated by cycle threshold (Ct) values. The Ct value of the target genes was normalized (ΔCt) to the Ct value of the GUS gene of the samples.The results were statistically analysed using ‘STATISTICA 8,0’. Statistical analysis was performed by means of Mann-Whitney’s U-test and p<0,05 indicated a significant difference. Overall survival (OS) was determined using Kaplan-Meier method. The long-rank test was used to compare the curves.
Results
In comparison to control group TLR2 and TLR4 mRNA expression was higher in B-CLL patients than in healthy individuals (ΔCt TLR2 6.46±9.58 vs 0.98±0.43 and ΔCt TLR4 11.91±70.22 vs 2.21±0.32)(p<0.05). TLR9 mRNA expression was higher in control group than in patients with B-CLL (ΔCt TLR9 23.65±16.29 vs 3.35±1.93)(p<0.05). We found that patients with higher mRNA expression of TLR9 had significantly longer OS than patients with lower mRNA expression of TLR9 (p<0.05).TLR2 mRNA expression was higher in patients with advanced-stage CLL (Rai stages III and IV) than in patients with early-stage disease (Rai stages 0-II) (ΔCt TLR2 19.10±17.76 vs 7.94±6.25) (p<0.05). Moreover we observed that expression of TLR2 in patients with anemia was significant higher than in patients without anemia (ΔCt TLR2 17.18±14.29 vs 7.10±5.98) (p<0.05).
Conclusion
In conclusion, our results suggest that TLRs could become new potential biological markers for the clinical outcome in patients with B-cell chronic lymphocytic leukemia. However, this observation should be validated by a larger study.
Session topic: E-poster
Keyword(s): B cell, Chronic lymphocytic leukemia
Type: Publication Only
Background
B-cell chronic lymphocytic leukemia (B-CLL) presents with progressive accumulation of monoclonal B-cells in the peripheral blood, bone marrow and lymphoid organs. B-CLL is characterized by heterogenous clinical outcome. Some patients have an indolent disease and the others have an aggressive clinical course of B-CLL. Toll-like receptors (TLRs) play an important role in B-cell activation and maturation and may be involved in the pathogenesis of B-cell lymphomas. TLRs are essential receptors of the innate immune system and key regulators of the acquired immune system. TLRs are mainly expressed in human immune related cells such as monocytes, neutrophils, macrophages, dendritic cells, T cells, B cells and NK cells. The expression of TLRs and their association with other prognostic factors in B-CLL patients remains unclear.
Aims
The aim of our study was to evaluate the expression of TLR2, TLR4 and TLR9 and their significance as biological markers in patients with B-cell chronic lymphocytic leukemia.
Methods
60 patients with newly diagnosed B-CLL were evaluated (29 females and 31 males). The median age of patients was 68 years (range: 52-88 years). The diagnosis was performed according to the IWCLL/NCI criteria for CLL. 40 patients (67%) had early-stage CLL (Rai stage 0-II) and 20 patients (33%) had advanced-stage CLL (Rai stage III and IV). All patients were either untreated. The healthy control group included 14 age-matched individuals (7 females and 7 males).Using quantitative reverse transcriptase PCR, the mRNA expression of genes TLR2, TLR4 and TLR9 was measured. The relative quantitation was indicated by cycle threshold (Ct) values. The Ct value of the target genes was normalized (ΔCt) to the Ct value of the GUS gene of the samples.The results were statistically analysed using ‘STATISTICA 8,0’. Statistical analysis was performed by means of Mann-Whitney’s U-test and p<0,05 indicated a significant difference. Overall survival (OS) was determined using Kaplan-Meier method. The long-rank test was used to compare the curves.
Results
In comparison to control group TLR2 and TLR4 mRNA expression was higher in B-CLL patients than in healthy individuals (ΔCt TLR2 6.46±9.58 vs 0.98±0.43 and ΔCt TLR4 11.91±70.22 vs 2.21±0.32)(p<0.05). TLR9 mRNA expression was higher in control group than in patients with B-CLL (ΔCt TLR9 23.65±16.29 vs 3.35±1.93)(p<0.05). We found that patients with higher mRNA expression of TLR9 had significantly longer OS than patients with lower mRNA expression of TLR9 (p<0.05).TLR2 mRNA expression was higher in patients with advanced-stage CLL (Rai stages III and IV) than in patients with early-stage disease (Rai stages 0-II) (ΔCt TLR2 19.10±17.76 vs 7.94±6.25) (p<0.05). Moreover we observed that expression of TLR2 in patients with anemia was significant higher than in patients without anemia (ΔCt TLR2 17.18±14.29 vs 7.10±5.98) (p<0.05).
Conclusion
In conclusion, our results suggest that TLRs could become new potential biological markers for the clinical outcome in patients with B-cell chronic lymphocytic leukemia. However, this observation should be validated by a larger study.
Session topic: E-poster
Keyword(s): B cell, Chronic lymphocytic leukemia
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