BACH2 & PRDM1: PREDICTIVE MARKERS OF IMMUNOSENESCENCE IN AGING?
(Abstract release date: 05/19/16)
EHA Library. BRON D. 06/09/16; 134680; PB1780
Prof. Dr. Dominique BRON
Contributions
Contributions
Abstract
Abstract: PB1780
Type: Publication Only
Background
Aging is characterized by a progressive decline in immune surveillance that favours cancer development. This is illustrated by the high median age of most malignant hemopathies. There is currently a lack of information related to genetic or epigenetic modifications of tumor suppressor genes (TSGs) in ageing immune cells. Our previous studies investigated the 6q deletion in T-cell lymphoproliferative diseases and we reported that BACH2 gene is a candidate TSGs.
Aims
In this study, we examined whether BACH2 and PRDM1 could be predictive markers of immunosenescence in lymphocytes subsets according to age.
Methods
Lymphocytes subsets were analysed using multi-colour flow cytometry to assess expression of CD45, CD3, CD4, CD8, CD45RA, CD25, CD197, CD19, CD27, CD5, CD56 and CD16. Lymphocyte subsets were isolated using the MACS isolation system for subsequent molecular investigations. BACH2 and PRDM1 were quantified by qRT-PCR and western blotting for each purified lymphocytes subset.
Results
Peripheral blood samples were obtained from 35 healthy donors (HDs) of different ages (20y to 90y), including 18 HDs under 50y (median: 36) and 17 HDs above 50y (median: 61). Absolute lymphocyte counts did not vary between these two groups but alterations in lymphocyte subsets distribution were detected. The number of naïve T cells and CD8+ cytotoxic T cells was significantly reduced in the older group (p=0.01 and 0.002). Our data confirmed that the CD4:CD8 ratio and effector T cells numbers are significantly increased (p<0.0001 and 0.01) with age.BACH2 and PRDM1 gene expression was studied by using qRT-PCR to evaluate 28 HDs [14 HDs under 50y (median: 38) and 14 HDs above 50y (median: 62)] compared with 23 untreated Chronic Lymphocytic Leukemia (CLL) patients (median age: 69). The purity of each lymphocytes subset was 95%>99%. BACH2 was significantly down-regulated in most lymphocytes subsets in the older group: CD4+, CD4+ naïve, CD8+ T cells and CD19+ B cells (p=0.001; 0.005; 0.004 and 0.03, respectively). Compared with a similar age group of HDs, BACH2 expression was even more severely reduced in CD19+, CD4+, CD8+ subsets of CLL patients (p=0.004; 0.001 and <0.001). In contrast, PRDM1 was significantly up-regulated in the CD4+ and CD8+ T cells (p=0.003; 0.001) of CLL patients but not in leukemic B cells. There was inverse correlation between BACH2 and PRDM1 (Pearson r=0.82; p<0.0001) in T cells of CLL patients. In addition, by using western blot BACH2 and BLIMP1 protein expression in CD4+, CD8+ and CD19+ lymphocytes correlated significantly with their transcripts expression levels. These observations uncover the roles of BACH2 and PRDM1 in the survival of immune cells in HD and CLL patients.
Conclusion
Our investigations suggest that BACH2 and PRDM1 expression is correlated with immunosenescence. Moreover, in CLL patients, this down regulation of BACH2 is even more pronounced. Further investigation should be conducted to better understand the role of unbalanced expression of BACH2 and PRDM1 genes in lymphocytes functions and survival.
Session topic: E-poster
Keyword(s): Elderly, Genetic instability, Immunodeficiency
Type: Publication Only
Background
Aging is characterized by a progressive decline in immune surveillance that favours cancer development. This is illustrated by the high median age of most malignant hemopathies. There is currently a lack of information related to genetic or epigenetic modifications of tumor suppressor genes (TSGs) in ageing immune cells. Our previous studies investigated the 6q deletion in T-cell lymphoproliferative diseases and we reported that BACH2 gene is a candidate TSGs.
Aims
In this study, we examined whether BACH2 and PRDM1 could be predictive markers of immunosenescence in lymphocytes subsets according to age.
Methods
Lymphocytes subsets were analysed using multi-colour flow cytometry to assess expression of CD45, CD3, CD4, CD8, CD45RA, CD25, CD197, CD19, CD27, CD5, CD56 and CD16. Lymphocyte subsets were isolated using the MACS isolation system for subsequent molecular investigations. BACH2 and PRDM1 were quantified by qRT-PCR and western blotting for each purified lymphocytes subset.
Results
Peripheral blood samples were obtained from 35 healthy donors (HDs) of different ages (20y to 90y), including 18 HDs under 50y (median: 36) and 17 HDs above 50y (median: 61). Absolute lymphocyte counts did not vary between these two groups but alterations in lymphocyte subsets distribution were detected. The number of naïve T cells and CD8+ cytotoxic T cells was significantly reduced in the older group (p=0.01 and 0.002). Our data confirmed that the CD4:CD8 ratio and effector T cells numbers are significantly increased (p<0.0001 and 0.01) with age.BACH2 and PRDM1 gene expression was studied by using qRT-PCR to evaluate 28 HDs [14 HDs under 50y (median: 38) and 14 HDs above 50y (median: 62)] compared with 23 untreated Chronic Lymphocytic Leukemia (CLL) patients (median age: 69). The purity of each lymphocytes subset was 95%>99%. BACH2 was significantly down-regulated in most lymphocytes subsets in the older group: CD4+, CD4+ naïve, CD8+ T cells and CD19+ B cells (p=0.001; 0.005; 0.004 and 0.03, respectively). Compared with a similar age group of HDs, BACH2 expression was even more severely reduced in CD19+, CD4+, CD8+ subsets of CLL patients (p=0.004; 0.001 and <0.001). In contrast, PRDM1 was significantly up-regulated in the CD4+ and CD8+ T cells (p=0.003; 0.001) of CLL patients but not in leukemic B cells. There was inverse correlation between BACH2 and PRDM1 (Pearson r=0.82; p<0.0001) in T cells of CLL patients. In addition, by using western blot BACH2 and BLIMP1 protein expression in CD4+, CD8+ and CD19+ lymphocytes correlated significantly with their transcripts expression levels. These observations uncover the roles of BACH2 and PRDM1 in the survival of immune cells in HD and CLL patients.
Conclusion
Our investigations suggest that BACH2 and PRDM1 expression is correlated with immunosenescence. Moreover, in CLL patients, this down regulation of BACH2 is even more pronounced. Further investigation should be conducted to better understand the role of unbalanced expression of BACH2 and PRDM1 genes in lymphocytes functions and survival.
Session topic: E-poster
Keyword(s): Elderly, Genetic instability, Immunodeficiency
Abstract: PB1780
Type: Publication Only
Background
Aging is characterized by a progressive decline in immune surveillance that favours cancer development. This is illustrated by the high median age of most malignant hemopathies. There is currently a lack of information related to genetic or epigenetic modifications of tumor suppressor genes (TSGs) in ageing immune cells. Our previous studies investigated the 6q deletion in T-cell lymphoproliferative diseases and we reported that BACH2 gene is a candidate TSGs.
Aims
In this study, we examined whether BACH2 and PRDM1 could be predictive markers of immunosenescence in lymphocytes subsets according to age.
Methods
Lymphocytes subsets were analysed using multi-colour flow cytometry to assess expression of CD45, CD3, CD4, CD8, CD45RA, CD25, CD197, CD19, CD27, CD5, CD56 and CD16. Lymphocyte subsets were isolated using the MACS isolation system for subsequent molecular investigations. BACH2 and PRDM1 were quantified by qRT-PCR and western blotting for each purified lymphocytes subset.
Results
Peripheral blood samples were obtained from 35 healthy donors (HDs) of different ages (20y to 90y), including 18 HDs under 50y (median: 36) and 17 HDs above 50y (median: 61). Absolute lymphocyte counts did not vary between these two groups but alterations in lymphocyte subsets distribution were detected. The number of naïve T cells and CD8+ cytotoxic T cells was significantly reduced in the older group (p=0.01 and 0.002). Our data confirmed that the CD4:CD8 ratio and effector T cells numbers are significantly increased (p<0.0001 and 0.01) with age.BACH2 and PRDM1 gene expression was studied by using qRT-PCR to evaluate 28 HDs [14 HDs under 50y (median: 38) and 14 HDs above 50y (median: 62)] compared with 23 untreated Chronic Lymphocytic Leukemia (CLL) patients (median age: 69). The purity of each lymphocytes subset was 95%>99%. BACH2 was significantly down-regulated in most lymphocytes subsets in the older group: CD4+, CD4+ naïve, CD8+ T cells and CD19+ B cells (p=0.001; 0.005; 0.004 and 0.03, respectively). Compared with a similar age group of HDs, BACH2 expression was even more severely reduced in CD19+, CD4+, CD8+ subsets of CLL patients (p=0.004; 0.001 and <0.001). In contrast, PRDM1 was significantly up-regulated in the CD4+ and CD8+ T cells (p=0.003; 0.001) of CLL patients but not in leukemic B cells. There was inverse correlation between BACH2 and PRDM1 (Pearson r=0.82; p<0.0001) in T cells of CLL patients. In addition, by using western blot BACH2 and BLIMP1 protein expression in CD4+, CD8+ and CD19+ lymphocytes correlated significantly with their transcripts expression levels. These observations uncover the roles of BACH2 and PRDM1 in the survival of immune cells in HD and CLL patients.
Conclusion
Our investigations suggest that BACH2 and PRDM1 expression is correlated with immunosenescence. Moreover, in CLL patients, this down regulation of BACH2 is even more pronounced. Further investigation should be conducted to better understand the role of unbalanced expression of BACH2 and PRDM1 genes in lymphocytes functions and survival.
Session topic: E-poster
Keyword(s): Elderly, Genetic instability, Immunodeficiency
Type: Publication Only
Background
Aging is characterized by a progressive decline in immune surveillance that favours cancer development. This is illustrated by the high median age of most malignant hemopathies. There is currently a lack of information related to genetic or epigenetic modifications of tumor suppressor genes (TSGs) in ageing immune cells. Our previous studies investigated the 6q deletion in T-cell lymphoproliferative diseases and we reported that BACH2 gene is a candidate TSGs.
Aims
In this study, we examined whether BACH2 and PRDM1 could be predictive markers of immunosenescence in lymphocytes subsets according to age.
Methods
Lymphocytes subsets were analysed using multi-colour flow cytometry to assess expression of CD45, CD3, CD4, CD8, CD45RA, CD25, CD197, CD19, CD27, CD5, CD56 and CD16. Lymphocyte subsets were isolated using the MACS isolation system for subsequent molecular investigations. BACH2 and PRDM1 were quantified by qRT-PCR and western blotting for each purified lymphocytes subset.
Results
Peripheral blood samples were obtained from 35 healthy donors (HDs) of different ages (20y to 90y), including 18 HDs under 50y (median: 36) and 17 HDs above 50y (median: 61). Absolute lymphocyte counts did not vary between these two groups but alterations in lymphocyte subsets distribution were detected. The number of naïve T cells and CD8+ cytotoxic T cells was significantly reduced in the older group (p=0.01 and 0.002). Our data confirmed that the CD4:CD8 ratio and effector T cells numbers are significantly increased (p<0.0001 and 0.01) with age.BACH2 and PRDM1 gene expression was studied by using qRT-PCR to evaluate 28 HDs [14 HDs under 50y (median: 38) and 14 HDs above 50y (median: 62)] compared with 23 untreated Chronic Lymphocytic Leukemia (CLL) patients (median age: 69). The purity of each lymphocytes subset was 95%>99%. BACH2 was significantly down-regulated in most lymphocytes subsets in the older group: CD4+, CD4+ naïve, CD8+ T cells and CD19+ B cells (p=0.001; 0.005; 0.004 and 0.03, respectively). Compared with a similar age group of HDs, BACH2 expression was even more severely reduced in CD19+, CD4+, CD8+ subsets of CLL patients (p=0.004; 0.001 and <0.001). In contrast, PRDM1 was significantly up-regulated in the CD4+ and CD8+ T cells (p=0.003; 0.001) of CLL patients but not in leukemic B cells. There was inverse correlation between BACH2 and PRDM1 (Pearson r=0.82; p<0.0001) in T cells of CLL patients. In addition, by using western blot BACH2 and BLIMP1 protein expression in CD4+, CD8+ and CD19+ lymphocytes correlated significantly with their transcripts expression levels. These observations uncover the roles of BACH2 and PRDM1 in the survival of immune cells in HD and CLL patients.
Conclusion
Our investigations suggest that BACH2 and PRDM1 expression is correlated with immunosenescence. Moreover, in CLL patients, this down regulation of BACH2 is even more pronounced. Further investigation should be conducted to better understand the role of unbalanced expression of BACH2 and PRDM1 genes in lymphocytes functions and survival.
Session topic: E-poster
Keyword(s): Elderly, Genetic instability, Immunodeficiency
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