Contributions
Abstract: PB1600
Type: Publication Only
Background
Acute lymphoblastic leukemia (ALL) comprises a group of aggressive and heterogeneous malignancies, occurring in adults and representing the most common pediatric cancer. Up to 25% of patients are genetically unclassified or have an intermediate prognosis; therefore, identifying novel biomarkers and therapeutic targets, as genetic and epigenetic changes, is critical to accurately allocate patients in risk groups. Epigenetic enzymes represent novel therapeutic targets in acute leukemia; however, their connections with prognosis markers across children or adult ALL patients remain unclear
Aims
In this study, we described that the expression of G9A correlates with VLA-4 (very late antigen-4), an integrin cell receptor that serves as a central mediator for the dissemination of ALL cells and as prognostic predictor in pediatric ALL.
Methods
We analyzed the expression of G9A, VLA-4 and SUV39H1 in 51 children patients (range 1-14 years) by RT-qPCR. Then we evaluated the correlation between the expression levels and clinical characteristics of the cohort. We also analyzed the cell migration by using in vitro Transwell experiments.
Results
We demonstrated a positive correlation between VLA-4 and G9A levels but not between VLA-4 and SUV39H1. Remarkably, we did not observe any VLA-4/G9A correlation in normal lymphocytes (n=10), suggesting a fundamental connection in leukemia cells. To determine the role of G9A in ALL cell migration, we quantified the levels of H3K9me3 during ALL cell migration. Effective migration induced higher levels of H3K9me3 in moving cells compared to their counterpart in the upper chamber of the Transwell. Moreover, BIX01294 treatment (a G9A inhibitor) impaired the ALL cell migration, suggesting a critical role for this enzyme during leukemia dissemination.
Conclusion
In summary, our results suggested a clinical potential interest of G9A, as its correlation with VLA-4 might open future targeting approaches and innovative drugs for children ALL patients.
Session topic: 1. Acute lymphoblastic leukemia – Biology & Translational Research
Keyword(s): Epigenetic, Integrin
Abstract: PB1600
Type: Publication Only
Background
Acute lymphoblastic leukemia (ALL) comprises a group of aggressive and heterogeneous malignancies, occurring in adults and representing the most common pediatric cancer. Up to 25% of patients are genetically unclassified or have an intermediate prognosis; therefore, identifying novel biomarkers and therapeutic targets, as genetic and epigenetic changes, is critical to accurately allocate patients in risk groups. Epigenetic enzymes represent novel therapeutic targets in acute leukemia; however, their connections with prognosis markers across children or adult ALL patients remain unclear
Aims
In this study, we described that the expression of G9A correlates with VLA-4 (very late antigen-4), an integrin cell receptor that serves as a central mediator for the dissemination of ALL cells and as prognostic predictor in pediatric ALL.
Methods
We analyzed the expression of G9A, VLA-4 and SUV39H1 in 51 children patients (range 1-14 years) by RT-qPCR. Then we evaluated the correlation between the expression levels and clinical characteristics of the cohort. We also analyzed the cell migration by using in vitro Transwell experiments.
Results
We demonstrated a positive correlation between VLA-4 and G9A levels but not between VLA-4 and SUV39H1. Remarkably, we did not observe any VLA-4/G9A correlation in normal lymphocytes (n=10), suggesting a fundamental connection in leukemia cells. To determine the role of G9A in ALL cell migration, we quantified the levels of H3K9me3 during ALL cell migration. Effective migration induced higher levels of H3K9me3 in moving cells compared to their counterpart in the upper chamber of the Transwell. Moreover, BIX01294 treatment (a G9A inhibitor) impaired the ALL cell migration, suggesting a critical role for this enzyme during leukemia dissemination.
Conclusion
In summary, our results suggested a clinical potential interest of G9A, as its correlation with VLA-4 might open future targeting approaches and innovative drugs for children ALL patients.
Session topic: 1. Acute lymphoblastic leukemia – Biology & Translational Research
Keyword(s): Epigenetic, Integrin