ATP11C IS DOWNREGULATED IN LEUKOCYTES AND RETICULOCYTES IN SICKLE CELL ANEMIA
(Abstract release date: 05/19/16)
EHA Library. Pereira-Martins D. 06/09/16; 133012; E1463
Mr. Diego Antonio Pereira-Martins
Contributions
Contributions
Abstract
Abstract: E1463
Type: Eposter Presentation
Background
In general, the phosphatidylserine (PS) exposure represents the major cause of blood cells adhesion to the vascular endothelium, and may contribute for vaso-occlusive crisis and extravascular hemolysis in beta-hemoglobinopathies, including sickle cell anemia (SCA). Such process may be potentiated by the SS-hemoglobin polymerization and significantly worsened in the absence of physiologic mechanism involved in PS internalization. In this context, members of the P4-type ATPase family constitute an important class of enzymes responsible for phospholipids translocation in plasma membrane, and several evidence suggests that the low expression of the ATP11C gene (a specific member of the P4-type ATPase family) is associated with higher rate of PS exposure in peripheral blood cells. Corroborating these data, the evaluation of erythropoiesis in ATP11C-deficient mice showed an abnormal shape of erythrocytes, lower rate of PS translocation, and shortened life span of mature erythrocytes, with consequent anemia. Therefore, it is conceivable that lower ATP11C transcripts levels may act as an important genetic modifier, increasing the PS exposure and, consequently, enhancing the adhesion of leukocytes, platelets, erythrocytes and vascular endothelial cells in SCA.
Aims
Here, we evaluated the gene expression profile of the ATP11C in granulocytes, mononuclear cells and reticulocytes from patients with SCA, beta-thalassemia and healthy donors. We also correlated these findings with the main chronic clinical complications in SCA.
Methods
Sixty-four patients with SCA (median age: 31 years, range, 15-61 years), with 35 male (55%), and fully characterized for βS-globin gene haplotype (bantu/bantu), and co-inheritance alpha-thalassemia (absence of -3.7kb deletion) were included. Total RNA from granulocytes, mononuclear cells, and reticulocytes was isolated. In addition, 14 patients with beta-thalassemia and 16 healthy donors (hemoglobin profile AA) were enrolled. ATP11C transcripts levels (Hs_00937051_m1) were analyzed by real-time quantitative PCR using the median value of GAPDH and 18S as endogenous control.
Results
First, we analyzed the ATP11C transcript levels in granulocytes, mononuclear cells and reticulocytes from patients with SCA. Reticulocytes presented lower levels of ATP11C transcripts (P<0.05). We next showed that the SCA reticulocytes had a lower ATP11C transcripts levels compared to beta-thalassemia and healthy donors reticulocytes (P<0.05). Of interest, ATP11C transcript levels were lower in both leukocytes (granulocytes and mononuclear) and reticulocytes from patients with SCA compared to healthy donors (P=0.023). According to the chronic clinical complications frequently reported in patients with SCA, 13 patients (20%) had leg ulcer solely, followed by cerebrovascular disease (7 patients; 11%). Twenty-one patients (33%) had more than one clinical complication (including osteonecrosis along with acute chest syndrome, and priapism), and 23 patients (36%) had no documented clinical complication. Patients who presented more than one clinical complication exhibited lower ATP11C transcripts levels (P<0.05).
Conclusion
Although limited number of patients and no validation data in an independent cohort constitute the main limitations of our study, our results showed that ATP11C transcript levels is decreased in SS-genotyped cells, in particular reticulocytes, and such decrease may be associated with higher rate of clinical complications in SCA.
Session topic: E-poster
Keyword(s): Hemoglobinopathy, Phosphatidylserine, Reticulocyte, Sickle cell anemia
Type: Eposter Presentation
Background
In general, the phosphatidylserine (PS) exposure represents the major cause of blood cells adhesion to the vascular endothelium, and may contribute for vaso-occlusive crisis and extravascular hemolysis in beta-hemoglobinopathies, including sickle cell anemia (SCA). Such process may be potentiated by the SS-hemoglobin polymerization and significantly worsened in the absence of physiologic mechanism involved in PS internalization. In this context, members of the P4-type ATPase family constitute an important class of enzymes responsible for phospholipids translocation in plasma membrane, and several evidence suggests that the low expression of the ATP11C gene (a specific member of the P4-type ATPase family) is associated with higher rate of PS exposure in peripheral blood cells. Corroborating these data, the evaluation of erythropoiesis in ATP11C-deficient mice showed an abnormal shape of erythrocytes, lower rate of PS translocation, and shortened life span of mature erythrocytes, with consequent anemia. Therefore, it is conceivable that lower ATP11C transcripts levels may act as an important genetic modifier, increasing the PS exposure and, consequently, enhancing the adhesion of leukocytes, platelets, erythrocytes and vascular endothelial cells in SCA.
Aims
Here, we evaluated the gene expression profile of the ATP11C in granulocytes, mononuclear cells and reticulocytes from patients with SCA, beta-thalassemia and healthy donors. We also correlated these findings with the main chronic clinical complications in SCA.
Methods
Sixty-four patients with SCA (median age: 31 years, range, 15-61 years), with 35 male (55%), and fully characterized for βS-globin gene haplotype (bantu/bantu), and co-inheritance alpha-thalassemia (absence of -3.7kb deletion) were included. Total RNA from granulocytes, mononuclear cells, and reticulocytes was isolated. In addition, 14 patients with beta-thalassemia and 16 healthy donors (hemoglobin profile AA) were enrolled. ATP11C transcripts levels (Hs_00937051_m1) were analyzed by real-time quantitative PCR using the median value of GAPDH and 18S as endogenous control.
Results
First, we analyzed the ATP11C transcript levels in granulocytes, mononuclear cells and reticulocytes from patients with SCA. Reticulocytes presented lower levels of ATP11C transcripts (P<0.05). We next showed that the SCA reticulocytes had a lower ATP11C transcripts levels compared to beta-thalassemia and healthy donors reticulocytes (P<0.05). Of interest, ATP11C transcript levels were lower in both leukocytes (granulocytes and mononuclear) and reticulocytes from patients with SCA compared to healthy donors (P=0.023). According to the chronic clinical complications frequently reported in patients with SCA, 13 patients (20%) had leg ulcer solely, followed by cerebrovascular disease (7 patients; 11%). Twenty-one patients (33%) had more than one clinical complication (including osteonecrosis along with acute chest syndrome, and priapism), and 23 patients (36%) had no documented clinical complication. Patients who presented more than one clinical complication exhibited lower ATP11C transcripts levels (P<0.05).
Conclusion
Although limited number of patients and no validation data in an independent cohort constitute the main limitations of our study, our results showed that ATP11C transcript levels is decreased in SS-genotyped cells, in particular reticulocytes, and such decrease may be associated with higher rate of clinical complications in SCA.
Session topic: E-poster
Keyword(s): Hemoglobinopathy, Phosphatidylserine, Reticulocyte, Sickle cell anemia
Abstract: E1463
Type: Eposter Presentation
Background
In general, the phosphatidylserine (PS) exposure represents the major cause of blood cells adhesion to the vascular endothelium, and may contribute for vaso-occlusive crisis and extravascular hemolysis in beta-hemoglobinopathies, including sickle cell anemia (SCA). Such process may be potentiated by the SS-hemoglobin polymerization and significantly worsened in the absence of physiologic mechanism involved in PS internalization. In this context, members of the P4-type ATPase family constitute an important class of enzymes responsible for phospholipids translocation in plasma membrane, and several evidence suggests that the low expression of the ATP11C gene (a specific member of the P4-type ATPase family) is associated with higher rate of PS exposure in peripheral blood cells. Corroborating these data, the evaluation of erythropoiesis in ATP11C-deficient mice showed an abnormal shape of erythrocytes, lower rate of PS translocation, and shortened life span of mature erythrocytes, with consequent anemia. Therefore, it is conceivable that lower ATP11C transcripts levels may act as an important genetic modifier, increasing the PS exposure and, consequently, enhancing the adhesion of leukocytes, platelets, erythrocytes and vascular endothelial cells in SCA.
Aims
Here, we evaluated the gene expression profile of the ATP11C in granulocytes, mononuclear cells and reticulocytes from patients with SCA, beta-thalassemia and healthy donors. We also correlated these findings with the main chronic clinical complications in SCA.
Methods
Sixty-four patients with SCA (median age: 31 years, range, 15-61 years), with 35 male (55%), and fully characterized for βS-globin gene haplotype (bantu/bantu), and co-inheritance alpha-thalassemia (absence of -3.7kb deletion) were included. Total RNA from granulocytes, mononuclear cells, and reticulocytes was isolated. In addition, 14 patients with beta-thalassemia and 16 healthy donors (hemoglobin profile AA) were enrolled. ATP11C transcripts levels (Hs_00937051_m1) were analyzed by real-time quantitative PCR using the median value of GAPDH and 18S as endogenous control.
Results
First, we analyzed the ATP11C transcript levels in granulocytes, mononuclear cells and reticulocytes from patients with SCA. Reticulocytes presented lower levels of ATP11C transcripts (P<0.05). We next showed that the SCA reticulocytes had a lower ATP11C transcripts levels compared to beta-thalassemia and healthy donors reticulocytes (P<0.05). Of interest, ATP11C transcript levels were lower in both leukocytes (granulocytes and mononuclear) and reticulocytes from patients with SCA compared to healthy donors (P=0.023). According to the chronic clinical complications frequently reported in patients with SCA, 13 patients (20%) had leg ulcer solely, followed by cerebrovascular disease (7 patients; 11%). Twenty-one patients (33%) had more than one clinical complication (including osteonecrosis along with acute chest syndrome, and priapism), and 23 patients (36%) had no documented clinical complication. Patients who presented more than one clinical complication exhibited lower ATP11C transcripts levels (P<0.05).
Conclusion
Although limited number of patients and no validation data in an independent cohort constitute the main limitations of our study, our results showed that ATP11C transcript levels is decreased in SS-genotyped cells, in particular reticulocytes, and such decrease may be associated with higher rate of clinical complications in SCA.
Session topic: E-poster
Keyword(s): Hemoglobinopathy, Phosphatidylserine, Reticulocyte, Sickle cell anemia
Type: Eposter Presentation
Background
In general, the phosphatidylserine (PS) exposure represents the major cause of blood cells adhesion to the vascular endothelium, and may contribute for vaso-occlusive crisis and extravascular hemolysis in beta-hemoglobinopathies, including sickle cell anemia (SCA). Such process may be potentiated by the SS-hemoglobin polymerization and significantly worsened in the absence of physiologic mechanism involved in PS internalization. In this context, members of the P4-type ATPase family constitute an important class of enzymes responsible for phospholipids translocation in plasma membrane, and several evidence suggests that the low expression of the ATP11C gene (a specific member of the P4-type ATPase family) is associated with higher rate of PS exposure in peripheral blood cells. Corroborating these data, the evaluation of erythropoiesis in ATP11C-deficient mice showed an abnormal shape of erythrocytes, lower rate of PS translocation, and shortened life span of mature erythrocytes, with consequent anemia. Therefore, it is conceivable that lower ATP11C transcripts levels may act as an important genetic modifier, increasing the PS exposure and, consequently, enhancing the adhesion of leukocytes, platelets, erythrocytes and vascular endothelial cells in SCA.
Aims
Here, we evaluated the gene expression profile of the ATP11C in granulocytes, mononuclear cells and reticulocytes from patients with SCA, beta-thalassemia and healthy donors. We also correlated these findings with the main chronic clinical complications in SCA.
Methods
Sixty-four patients with SCA (median age: 31 years, range, 15-61 years), with 35 male (55%), and fully characterized for βS-globin gene haplotype (bantu/bantu), and co-inheritance alpha-thalassemia (absence of -3.7kb deletion) were included. Total RNA from granulocytes, mononuclear cells, and reticulocytes was isolated. In addition, 14 patients with beta-thalassemia and 16 healthy donors (hemoglobin profile AA) were enrolled. ATP11C transcripts levels (Hs_00937051_m1) were analyzed by real-time quantitative PCR using the median value of GAPDH and 18S as endogenous control.
Results
First, we analyzed the ATP11C transcript levels in granulocytes, mononuclear cells and reticulocytes from patients with SCA. Reticulocytes presented lower levels of ATP11C transcripts (P<0.05). We next showed that the SCA reticulocytes had a lower ATP11C transcripts levels compared to beta-thalassemia and healthy donors reticulocytes (P<0.05). Of interest, ATP11C transcript levels were lower in both leukocytes (granulocytes and mononuclear) and reticulocytes from patients with SCA compared to healthy donors (P=0.023). According to the chronic clinical complications frequently reported in patients with SCA, 13 patients (20%) had leg ulcer solely, followed by cerebrovascular disease (7 patients; 11%). Twenty-one patients (33%) had more than one clinical complication (including osteonecrosis along with acute chest syndrome, and priapism), and 23 patients (36%) had no documented clinical complication. Patients who presented more than one clinical complication exhibited lower ATP11C transcripts levels (P<0.05).
Conclusion
Although limited number of patients and no validation data in an independent cohort constitute the main limitations of our study, our results showed that ATP11C transcript levels is decreased in SS-genotyped cells, in particular reticulocytes, and such decrease may be associated with higher rate of clinical complications in SCA.
Session topic: E-poster
Keyword(s): Hemoglobinopathy, Phosphatidylserine, Reticulocyte, Sickle cell anemia
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