INSULIN-LIKE GROWTH FACTOR SYSTEM AS A PROGNOSTIC BIOMARKER IN CHRONIC LYMPHOCYTIC LEUKEMIA: A CROSS-SECTIONAL STUDY
(Abstract release date: 05/19/16)
EHA Library. Lekka A. 06/09/16; 134691; PB1791
Prof. Dr. Antigoni Lekka
Contributions
Contributions
Abstract
Abstract: PB1791
Type: Publication Only
Background
B-cell chronic lymphocytic leukemia (B-CLL) is characterized by the accumulation of long-survived B lymphocytes arrested in G0/1 phase by impaired apoptosis. Growth factors may contribute to paracrine or autocrine loops affecting CLL cell survival via the induction of apoptosis-related genes. Insulin-like growth factor I (IGF-I), which is mainly produced by hepatocytes, constitutes an important anti-apoptotic factor for several malignant cells. Furthermore, IGF-I and its main binding protein IGFBP3 are related to the development and pathogenesis of insulin resistance, diabetes as well as in obesity-associated malignancies.
Aims
The goal of the present study was to evaluate circulating levels of IGF-I and IGFBP3 in patients suffering from B-CLL and control participants. We also explored the ratio of IGF-I/IGFBP3, which gives a mechanistic insight into IGF-I bioavailability, as well as IGF-I and IGFBP3 as prognostic parameters of B-CLL
Methods
Blood samples were collected from ninety five cases with incident B-CLL and an equal number of hospital controls, admitted for non-neoplastic and non-infectious conditions, matched on gender, age and year/month of diagnosis (±1 month) between 2001 and 2007. Informed consent was obtained from all study participants. Serum IGF-I and IGFBP3 were determined using commercially available ELISA assays (DIAsource ImmunoAssays S.A, Louvain-la-Neuve, Belgium). Moreover, serum lactate dehydrogenase (LDH), β2-microglobulin (BMG), lymphocyte morphology and the surface expression of CD38 in >30% of B-CLL lymphocytes were assessed. Statistical analysis of the data was performed using univariate and multivariate analyses with IBM-SPSS® version 23 for Windows.
Results
Overall, B-CLL patients had a significantly elevated body mass index (BMI) as compared to control participants (27.8 vs. 26.7 kg/m2; p<0.01). In univariate analysis, circulating levels of IGF-I were similar in cases compared to controls (126.75 ± 21.41 versus 125.10 ± 25.50 ng/mL, respectively, p=0.63). However, serum IGFBP3 was significantly lower in cases than controls (3.16 ± 0.96 versus 4.22 ± 1.03 μg/mL, respectively, p<0.001) while the IGF-I/IGFBP3 ratio was significantly elevated in cases compared to controls (0.049 ± 0.07 versus 0.030 ± 0.05, respectively, p=0.01). Lower serum IGFBP3 levels were associated with B-CLL risk in multivariable analyses adjusting for age, gender, date of diagnosis, family history of lymphohemopoietic cancer, BMI, serum IGF-I and insulin (<0.001). In B-CLL patients, serum IGF-I was significantly and positively associated with Binet stage, IGFBP3, LDH and BMG (p<0.001), and negatively associated with age (p<0.001).
Conclusion
The observed results highlight the potential involvement of IGF-I bioavailability in the B-CLL pathogenetic process. Circulating IGF-I might be a potential biomarker for B-CLL prognosis. Further prospective and longitudinal studies are needed in order to confirm these observations as well as to elucidate the contribution of the IGF-I system in B-CLL progression.
Session topic: E-poster
Keyword(s): B lymphocyte, Chronic lymphocytic leukemia, Growth factor, Obesity
Type: Publication Only
Background
B-cell chronic lymphocytic leukemia (B-CLL) is characterized by the accumulation of long-survived B lymphocytes arrested in G0/1 phase by impaired apoptosis. Growth factors may contribute to paracrine or autocrine loops affecting CLL cell survival via the induction of apoptosis-related genes. Insulin-like growth factor I (IGF-I), which is mainly produced by hepatocytes, constitutes an important anti-apoptotic factor for several malignant cells. Furthermore, IGF-I and its main binding protein IGFBP3 are related to the development and pathogenesis of insulin resistance, diabetes as well as in obesity-associated malignancies.
Aims
The goal of the present study was to evaluate circulating levels of IGF-I and IGFBP3 in patients suffering from B-CLL and control participants. We also explored the ratio of IGF-I/IGFBP3, which gives a mechanistic insight into IGF-I bioavailability, as well as IGF-I and IGFBP3 as prognostic parameters of B-CLL
Methods
Blood samples were collected from ninety five cases with incident B-CLL and an equal number of hospital controls, admitted for non-neoplastic and non-infectious conditions, matched on gender, age and year/month of diagnosis (±1 month) between 2001 and 2007. Informed consent was obtained from all study participants. Serum IGF-I and IGFBP3 were determined using commercially available ELISA assays (DIAsource ImmunoAssays S.A, Louvain-la-Neuve, Belgium). Moreover, serum lactate dehydrogenase (LDH), β2-microglobulin (BMG), lymphocyte morphology and the surface expression of CD38 in >30% of B-CLL lymphocytes were assessed. Statistical analysis of the data was performed using univariate and multivariate analyses with IBM-SPSS® version 23 for Windows.
Results
Overall, B-CLL patients had a significantly elevated body mass index (BMI) as compared to control participants (27.8 vs. 26.7 kg/m2; p<0.01). In univariate analysis, circulating levels of IGF-I were similar in cases compared to controls (126.75 ± 21.41 versus 125.10 ± 25.50 ng/mL, respectively, p=0.63). However, serum IGFBP3 was significantly lower in cases than controls (3.16 ± 0.96 versus 4.22 ± 1.03 μg/mL, respectively, p<0.001) while the IGF-I/IGFBP3 ratio was significantly elevated in cases compared to controls (0.049 ± 0.07 versus 0.030 ± 0.05, respectively, p=0.01). Lower serum IGFBP3 levels were associated with B-CLL risk in multivariable analyses adjusting for age, gender, date of diagnosis, family history of lymphohemopoietic cancer, BMI, serum IGF-I and insulin (<0.001). In B-CLL patients, serum IGF-I was significantly and positively associated with Binet stage, IGFBP3, LDH and BMG (p<0.001), and negatively associated with age (p<0.001).
Conclusion
The observed results highlight the potential involvement of IGF-I bioavailability in the B-CLL pathogenetic process. Circulating IGF-I might be a potential biomarker for B-CLL prognosis. Further prospective and longitudinal studies are needed in order to confirm these observations as well as to elucidate the contribution of the IGF-I system in B-CLL progression.
Session topic: E-poster
Keyword(s): B lymphocyte, Chronic lymphocytic leukemia, Growth factor, Obesity
Abstract: PB1791
Type: Publication Only
Background
B-cell chronic lymphocytic leukemia (B-CLL) is characterized by the accumulation of long-survived B lymphocytes arrested in G0/1 phase by impaired apoptosis. Growth factors may contribute to paracrine or autocrine loops affecting CLL cell survival via the induction of apoptosis-related genes. Insulin-like growth factor I (IGF-I), which is mainly produced by hepatocytes, constitutes an important anti-apoptotic factor for several malignant cells. Furthermore, IGF-I and its main binding protein IGFBP3 are related to the development and pathogenesis of insulin resistance, diabetes as well as in obesity-associated malignancies.
Aims
The goal of the present study was to evaluate circulating levels of IGF-I and IGFBP3 in patients suffering from B-CLL and control participants. We also explored the ratio of IGF-I/IGFBP3, which gives a mechanistic insight into IGF-I bioavailability, as well as IGF-I and IGFBP3 as prognostic parameters of B-CLL
Methods
Blood samples were collected from ninety five cases with incident B-CLL and an equal number of hospital controls, admitted for non-neoplastic and non-infectious conditions, matched on gender, age and year/month of diagnosis (±1 month) between 2001 and 2007. Informed consent was obtained from all study participants. Serum IGF-I and IGFBP3 were determined using commercially available ELISA assays (DIAsource ImmunoAssays S.A, Louvain-la-Neuve, Belgium). Moreover, serum lactate dehydrogenase (LDH), β2-microglobulin (BMG), lymphocyte morphology and the surface expression of CD38 in >30% of B-CLL lymphocytes were assessed. Statistical analysis of the data was performed using univariate and multivariate analyses with IBM-SPSS® version 23 for Windows.
Results
Overall, B-CLL patients had a significantly elevated body mass index (BMI) as compared to control participants (27.8 vs. 26.7 kg/m2; p<0.01). In univariate analysis, circulating levels of IGF-I were similar in cases compared to controls (126.75 ± 21.41 versus 125.10 ± 25.50 ng/mL, respectively, p=0.63). However, serum IGFBP3 was significantly lower in cases than controls (3.16 ± 0.96 versus 4.22 ± 1.03 μg/mL, respectively, p<0.001) while the IGF-I/IGFBP3 ratio was significantly elevated in cases compared to controls (0.049 ± 0.07 versus 0.030 ± 0.05, respectively, p=0.01). Lower serum IGFBP3 levels were associated with B-CLL risk in multivariable analyses adjusting for age, gender, date of diagnosis, family history of lymphohemopoietic cancer, BMI, serum IGF-I and insulin (<0.001). In B-CLL patients, serum IGF-I was significantly and positively associated with Binet stage, IGFBP3, LDH and BMG (p<0.001), and negatively associated with age (p<0.001).
Conclusion
The observed results highlight the potential involvement of IGF-I bioavailability in the B-CLL pathogenetic process. Circulating IGF-I might be a potential biomarker for B-CLL prognosis. Further prospective and longitudinal studies are needed in order to confirm these observations as well as to elucidate the contribution of the IGF-I system in B-CLL progression.
Session topic: E-poster
Keyword(s): B lymphocyte, Chronic lymphocytic leukemia, Growth factor, Obesity
Type: Publication Only
Background
B-cell chronic lymphocytic leukemia (B-CLL) is characterized by the accumulation of long-survived B lymphocytes arrested in G0/1 phase by impaired apoptosis. Growth factors may contribute to paracrine or autocrine loops affecting CLL cell survival via the induction of apoptosis-related genes. Insulin-like growth factor I (IGF-I), which is mainly produced by hepatocytes, constitutes an important anti-apoptotic factor for several malignant cells. Furthermore, IGF-I and its main binding protein IGFBP3 are related to the development and pathogenesis of insulin resistance, diabetes as well as in obesity-associated malignancies.
Aims
The goal of the present study was to evaluate circulating levels of IGF-I and IGFBP3 in patients suffering from B-CLL and control participants. We also explored the ratio of IGF-I/IGFBP3, which gives a mechanistic insight into IGF-I bioavailability, as well as IGF-I and IGFBP3 as prognostic parameters of B-CLL
Methods
Blood samples were collected from ninety five cases with incident B-CLL and an equal number of hospital controls, admitted for non-neoplastic and non-infectious conditions, matched on gender, age and year/month of diagnosis (±1 month) between 2001 and 2007. Informed consent was obtained from all study participants. Serum IGF-I and IGFBP3 were determined using commercially available ELISA assays (DIAsource ImmunoAssays S.A, Louvain-la-Neuve, Belgium). Moreover, serum lactate dehydrogenase (LDH), β2-microglobulin (BMG), lymphocyte morphology and the surface expression of CD38 in >30% of B-CLL lymphocytes were assessed. Statistical analysis of the data was performed using univariate and multivariate analyses with IBM-SPSS® version 23 for Windows.
Results
Overall, B-CLL patients had a significantly elevated body mass index (BMI) as compared to control participants (27.8 vs. 26.7 kg/m2; p<0.01). In univariate analysis, circulating levels of IGF-I were similar in cases compared to controls (126.75 ± 21.41 versus 125.10 ± 25.50 ng/mL, respectively, p=0.63). However, serum IGFBP3 was significantly lower in cases than controls (3.16 ± 0.96 versus 4.22 ± 1.03 μg/mL, respectively, p<0.001) while the IGF-I/IGFBP3 ratio was significantly elevated in cases compared to controls (0.049 ± 0.07 versus 0.030 ± 0.05, respectively, p=0.01). Lower serum IGFBP3 levels were associated with B-CLL risk in multivariable analyses adjusting for age, gender, date of diagnosis, family history of lymphohemopoietic cancer, BMI, serum IGF-I and insulin (<0.001). In B-CLL patients, serum IGF-I was significantly and positively associated with Binet stage, IGFBP3, LDH and BMG (p<0.001), and negatively associated with age (p<0.001).
Conclusion
The observed results highlight the potential involvement of IGF-I bioavailability in the B-CLL pathogenetic process. Circulating IGF-I might be a potential biomarker for B-CLL prognosis. Further prospective and longitudinal studies are needed in order to confirm these observations as well as to elucidate the contribution of the IGF-I system in B-CLL progression.
Session topic: E-poster
Keyword(s): B lymphocyte, Chronic lymphocytic leukemia, Growth factor, Obesity
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