OVEREXPRESSION OF ADAM28 ENHANCES ACUTE MYELOID LEUKEMIC CELL MIGRATION AND INCREASES THE GROWTH OF XENOGRAFT TUMOURS IN MICE
(Abstract release date: 05/19/16)
EHA Library. Su Y. 06/09/16; 132462; E913
Prof. Yan Su
Contributions
Contributions
Abstract
Abstract: E913
Type: Eposter Presentation
Background
Acute myeloid leukemia(AML) is fatal as a result of primaryrefractoriness, relapse, or treatment-related mortality. Cytogenetics is the most powerful predictor of prognosis in AML, and integrating additional genetic data may further improve predictive capabilities. A disintegrin and metalloproteinases (ADAMs) are involved in various biological events, including cell adhesion, cell fusion, membrane protein shedding, and proteolysis.Our previous study has demonstrated that the expression level of ADAM28 is significantly elevated in relapsed ALL patients and is regulated via a PI3K/Akt signalling pathway.We hypothesized that overexpression of ADAM28 might contribute to invasion and metastasis in adult AML, promoting thetumourigenicity potential andproliferation of AML cells.
Aims
To investigate whether overexpression of ADAM28 was associated with relapse in de novo AML patients, we performed this prospective clinical study and explored the functions and regulation of ADAM28 overexpression in vitro.
Methods
The mRNA expression of ADAMs in the bone marrow of de novo AMLpatients was measured by qPCR. ADAM28 expression levels in BM, serum and cerebrospinal fluid were also measured. Twenty-three healthy donors as controls and 200 AML patientswere included in our group. The cumulative incidence of relapse (CIR),overall survival (OS) and event-free survival (EFS) after a 3-year follow-up were used to evaluate prognosis.Primary AML cells and different AML cell lines were cultured to examine the expression of ADAM28 in vitro. ADAM28-specific cDNA and siRNA were designed and established.Leukemic cell migration was measured using modified Boydenchambers.A nude mouse model was established to measure the effect of ADAM28 on thetumourigenicity of leukemic cells in vivo. The expression of Ki-67 and PCNA was detected to measure proliferation.
Results
In general, mRNA expression of ADAM28 displayed the most significant differences between patients and healthy donors among the ADAMs detected.The expression of ADAM28 was significantly increased in AML patients compared with healthy donors. Patients suffering relapse exhibited significantly higher expression levels of ADAM28 compared with those who remained in complete remission. Patients with CNSL also demonstrated significantly increased ADAM28 expression in the CSF and serum compared with non-CNSL patients. The Kaplan–Meier survival curve showed that EFS was shorter andCIR was higher in patients with high expression levels of ADAM28.The results showed that age, karyotype and ADAM28 level are independent risk factors for OS and EFS.In vitro, the expression of ADAM28 was relatively higher in primary blast cells and SHI-1 cells, which were selected forsubsequentprocedures. Overexpression of ADAM28 promoted the proliferation and invasiveness of SHI-1 cells and primary blast cells transfected with ADAM28 cDNA; in contrast, knockdown of ADAM28 expression inhibitedproliferation and invasiveness.Following subcutaneous injection into nude mice,ADAM28 knock-down cells displayed an inhibited tumourigenicity potential, whereas ADAM28-overexpressingcells presented largerxenograft tumours.
Conclusion
Our findingsdemonstrate that overexpression of ADAM28 in AML patients is correlated to relapse; patients with higher levels of ADAM28 have a higher CIR. Overexpression of ADAM28 can enhance cell proliferation and migration, as well as tumourigenicity. These data suggest that ADAM28 may be a novel biomarker for predicting the prognosis of AML, potentially providing a new therapeutic target.
Session topic: E-poster
Keyword(s): Acute myeloid leukemia, Migration, Prognosis
Type: Eposter Presentation
Background
Acute myeloid leukemia(AML) is fatal as a result of primaryrefractoriness, relapse, or treatment-related mortality. Cytogenetics is the most powerful predictor of prognosis in AML, and integrating additional genetic data may further improve predictive capabilities. A disintegrin and metalloproteinases (ADAMs) are involved in various biological events, including cell adhesion, cell fusion, membrane protein shedding, and proteolysis.Our previous study has demonstrated that the expression level of ADAM28 is significantly elevated in relapsed ALL patients and is regulated via a PI3K/Akt signalling pathway.We hypothesized that overexpression of ADAM28 might contribute to invasion and metastasis in adult AML, promoting thetumourigenicity potential andproliferation of AML cells.
Aims
To investigate whether overexpression of ADAM28 was associated with relapse in de novo AML patients, we performed this prospective clinical study and explored the functions and regulation of ADAM28 overexpression in vitro.
Methods
The mRNA expression of ADAMs in the bone marrow of de novo AMLpatients was measured by qPCR. ADAM28 expression levels in BM, serum and cerebrospinal fluid were also measured. Twenty-three healthy donors as controls and 200 AML patientswere included in our group. The cumulative incidence of relapse (CIR),overall survival (OS) and event-free survival (EFS) after a 3-year follow-up were used to evaluate prognosis.Primary AML cells and different AML cell lines were cultured to examine the expression of ADAM28 in vitro. ADAM28-specific cDNA and siRNA were designed and established.Leukemic cell migration was measured using modified Boydenchambers.A nude mouse model was established to measure the effect of ADAM28 on thetumourigenicity of leukemic cells in vivo. The expression of Ki-67 and PCNA was detected to measure proliferation.
Results
In general, mRNA expression of ADAM28 displayed the most significant differences between patients and healthy donors among the ADAMs detected.The expression of ADAM28 was significantly increased in AML patients compared with healthy donors. Patients suffering relapse exhibited significantly higher expression levels of ADAM28 compared with those who remained in complete remission. Patients with CNSL also demonstrated significantly increased ADAM28 expression in the CSF and serum compared with non-CNSL patients. The Kaplan–Meier survival curve showed that EFS was shorter andCIR was higher in patients with high expression levels of ADAM28.The results showed that age, karyotype and ADAM28 level are independent risk factors for OS and EFS.In vitro, the expression of ADAM28 was relatively higher in primary blast cells and SHI-1 cells, which were selected forsubsequentprocedures. Overexpression of ADAM28 promoted the proliferation and invasiveness of SHI-1 cells and primary blast cells transfected with ADAM28 cDNA; in contrast, knockdown of ADAM28 expression inhibitedproliferation and invasiveness.Following subcutaneous injection into nude mice,ADAM28 knock-down cells displayed an inhibited tumourigenicity potential, whereas ADAM28-overexpressingcells presented largerxenograft tumours.
Conclusion
Our findingsdemonstrate that overexpression of ADAM28 in AML patients is correlated to relapse; patients with higher levels of ADAM28 have a higher CIR. Overexpression of ADAM28 can enhance cell proliferation and migration, as well as tumourigenicity. These data suggest that ADAM28 may be a novel biomarker for predicting the prognosis of AML, potentially providing a new therapeutic target.
Session topic: E-poster
Keyword(s): Acute myeloid leukemia, Migration, Prognosis
Abstract: E913
Type: Eposter Presentation
Background
Acute myeloid leukemia(AML) is fatal as a result of primaryrefractoriness, relapse, or treatment-related mortality. Cytogenetics is the most powerful predictor of prognosis in AML, and integrating additional genetic data may further improve predictive capabilities. A disintegrin and metalloproteinases (ADAMs) are involved in various biological events, including cell adhesion, cell fusion, membrane protein shedding, and proteolysis.Our previous study has demonstrated that the expression level of ADAM28 is significantly elevated in relapsed ALL patients and is regulated via a PI3K/Akt signalling pathway.We hypothesized that overexpression of ADAM28 might contribute to invasion and metastasis in adult AML, promoting thetumourigenicity potential andproliferation of AML cells.
Aims
To investigate whether overexpression of ADAM28 was associated with relapse in de novo AML patients, we performed this prospective clinical study and explored the functions and regulation of ADAM28 overexpression in vitro.
Methods
The mRNA expression of ADAMs in the bone marrow of de novo AMLpatients was measured by qPCR. ADAM28 expression levels in BM, serum and cerebrospinal fluid were also measured. Twenty-three healthy donors as controls and 200 AML patientswere included in our group. The cumulative incidence of relapse (CIR),overall survival (OS) and event-free survival (EFS) after a 3-year follow-up were used to evaluate prognosis.Primary AML cells and different AML cell lines were cultured to examine the expression of ADAM28 in vitro. ADAM28-specific cDNA and siRNA were designed and established.Leukemic cell migration was measured using modified Boydenchambers.A nude mouse model was established to measure the effect of ADAM28 on thetumourigenicity of leukemic cells in vivo. The expression of Ki-67 and PCNA was detected to measure proliferation.
Results
In general, mRNA expression of ADAM28 displayed the most significant differences between patients and healthy donors among the ADAMs detected.The expression of ADAM28 was significantly increased in AML patients compared with healthy donors. Patients suffering relapse exhibited significantly higher expression levels of ADAM28 compared with those who remained in complete remission. Patients with CNSL also demonstrated significantly increased ADAM28 expression in the CSF and serum compared with non-CNSL patients. The Kaplan–Meier survival curve showed that EFS was shorter andCIR was higher in patients with high expression levels of ADAM28.The results showed that age, karyotype and ADAM28 level are independent risk factors for OS and EFS.In vitro, the expression of ADAM28 was relatively higher in primary blast cells and SHI-1 cells, which were selected forsubsequentprocedures. Overexpression of ADAM28 promoted the proliferation and invasiveness of SHI-1 cells and primary blast cells transfected with ADAM28 cDNA; in contrast, knockdown of ADAM28 expression inhibitedproliferation and invasiveness.Following subcutaneous injection into nude mice,ADAM28 knock-down cells displayed an inhibited tumourigenicity potential, whereas ADAM28-overexpressingcells presented largerxenograft tumours.
Conclusion
Our findingsdemonstrate that overexpression of ADAM28 in AML patients is correlated to relapse; patients with higher levels of ADAM28 have a higher CIR. Overexpression of ADAM28 can enhance cell proliferation and migration, as well as tumourigenicity. These data suggest that ADAM28 may be a novel biomarker for predicting the prognosis of AML, potentially providing a new therapeutic target.
Session topic: E-poster
Keyword(s): Acute myeloid leukemia, Migration, Prognosis
Type: Eposter Presentation
Background
Acute myeloid leukemia(AML) is fatal as a result of primaryrefractoriness, relapse, or treatment-related mortality. Cytogenetics is the most powerful predictor of prognosis in AML, and integrating additional genetic data may further improve predictive capabilities. A disintegrin and metalloproteinases (ADAMs) are involved in various biological events, including cell adhesion, cell fusion, membrane protein shedding, and proteolysis.Our previous study has demonstrated that the expression level of ADAM28 is significantly elevated in relapsed ALL patients and is regulated via a PI3K/Akt signalling pathway.We hypothesized that overexpression of ADAM28 might contribute to invasion and metastasis in adult AML, promoting thetumourigenicity potential andproliferation of AML cells.
Aims
To investigate whether overexpression of ADAM28 was associated with relapse in de novo AML patients, we performed this prospective clinical study and explored the functions and regulation of ADAM28 overexpression in vitro.
Methods
The mRNA expression of ADAMs in the bone marrow of de novo AMLpatients was measured by qPCR. ADAM28 expression levels in BM, serum and cerebrospinal fluid were also measured. Twenty-three healthy donors as controls and 200 AML patientswere included in our group. The cumulative incidence of relapse (CIR),overall survival (OS) and event-free survival (EFS) after a 3-year follow-up were used to evaluate prognosis.Primary AML cells and different AML cell lines were cultured to examine the expression of ADAM28 in vitro. ADAM28-specific cDNA and siRNA were designed and established.Leukemic cell migration was measured using modified Boydenchambers.A nude mouse model was established to measure the effect of ADAM28 on thetumourigenicity of leukemic cells in vivo. The expression of Ki-67 and PCNA was detected to measure proliferation.
Results
In general, mRNA expression of ADAM28 displayed the most significant differences between patients and healthy donors among the ADAMs detected.The expression of ADAM28 was significantly increased in AML patients compared with healthy donors. Patients suffering relapse exhibited significantly higher expression levels of ADAM28 compared with those who remained in complete remission. Patients with CNSL also demonstrated significantly increased ADAM28 expression in the CSF and serum compared with non-CNSL patients. The Kaplan–Meier survival curve showed that EFS was shorter andCIR was higher in patients with high expression levels of ADAM28.The results showed that age, karyotype and ADAM28 level are independent risk factors for OS and EFS.In vitro, the expression of ADAM28 was relatively higher in primary blast cells and SHI-1 cells, which were selected forsubsequentprocedures. Overexpression of ADAM28 promoted the proliferation and invasiveness of SHI-1 cells and primary blast cells transfected with ADAM28 cDNA; in contrast, knockdown of ADAM28 expression inhibitedproliferation and invasiveness.Following subcutaneous injection into nude mice,ADAM28 knock-down cells displayed an inhibited tumourigenicity potential, whereas ADAM28-overexpressingcells presented largerxenograft tumours.
Conclusion
Our findingsdemonstrate that overexpression of ADAM28 in AML patients is correlated to relapse; patients with higher levels of ADAM28 have a higher CIR. Overexpression of ADAM28 can enhance cell proliferation and migration, as well as tumourigenicity. These data suggest that ADAM28 may be a novel biomarker for predicting the prognosis of AML, potentially providing a new therapeutic target.
Session topic: E-poster
Keyword(s): Acute myeloid leukemia, Migration, Prognosis
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