ROLE OF G9A AND EPIGENETIC CHANGES IN LEUKEMIA CELL MIGRATION AND THEIR REGULATION BY VLA4 INTEGRIN.
(Abstract release date: 05/19/16)
EHA Library. Redondo Munoz J. 06/09/16; 132388; E839
Dr. Javier Redondo Munoz
Contributions
Contributions
Abstract
Abstract: E839
Type: Eposter Presentation
Background
T-Acute Lymphoblastic Leukemia (T-ALL) originates from neoplastic T cell precursors in the thymus. Usually, T-ALL cells have to migrate from the thymus into other tissues, where residual cells might persist after treatments. The nuclear deformability of these tumor cells, and the signals from the cell receptors called integrins are critical to allow cancer cells to squeeze and cross physical barriers. Epigenetics, a novel cancer hallmark that comprises histone modification, histone variants and DNA modifications, leads a new drug generation to prime cancer cells to death. But some epigenetic changes, such as H3K9me3, have been linked with cancer invasion, and might have additional functions leading cancer progression.
Aims
The objective of this study was to explore how epigenetic changes induced by the integrin VLA4/α4β1 control, in a transcriptional independent manner, the nuclear deformability and infiltration of ALL cells.
Methods
Human T (Jurkat) leukemia cell lines, and normal primary T cells were cultured in suspension or on integrin ligands for different times and the levels of H3K9me3 were determined. Nuclear deformability was evaluated using several biophysical techniques, such as Atomic Force Microscopy. To identify the molecular mechanism induced by α4β1 integrin, and how this would be relevant for T-ALL cell migration, different biochemical and cell biology methods were performed.
Results
We showed that acute lymphoblastic leukemia (ALL) cells cultured on VCAM1 or Fibronectin (ligands of α4β1 integrin) presented higher levels of H3K9me3 than cells in suspension. We confirmed that ALL cells were more sensitive to this effect than normal T-cells. We determined that G9a, a histone methyltransferase, localized at the nuclear envelope and was responsible for H3K9 methylation when T-ALL cells were cultured on VCAM1. We used stable Jurkat cells depleted for G9a to demonstrate that H3K9 methylation contributed to the nuclear stiffness and the ability of ALL cells to migrate in response to chemotaxis and in 2D and 3D environments.
Conclusion
Our results reveal novel functions for G9a in modulating ALL migration, which might contribute to tumor cell dissemination and leukaemia progression.
Session topic: E-poster
Keyword(s): Acute lymphoblastic leukemia, Epigenetic, Integrin, Migration
Type: Eposter Presentation
Background
T-Acute Lymphoblastic Leukemia (T-ALL) originates from neoplastic T cell precursors in the thymus. Usually, T-ALL cells have to migrate from the thymus into other tissues, where residual cells might persist after treatments. The nuclear deformability of these tumor cells, and the signals from the cell receptors called integrins are critical to allow cancer cells to squeeze and cross physical barriers. Epigenetics, a novel cancer hallmark that comprises histone modification, histone variants and DNA modifications, leads a new drug generation to prime cancer cells to death. But some epigenetic changes, such as H3K9me3, have been linked with cancer invasion, and might have additional functions leading cancer progression.
Aims
The objective of this study was to explore how epigenetic changes induced by the integrin VLA4/α4β1 control, in a transcriptional independent manner, the nuclear deformability and infiltration of ALL cells.
Methods
Human T (Jurkat) leukemia cell lines, and normal primary T cells were cultured in suspension or on integrin ligands for different times and the levels of H3K9me3 were determined. Nuclear deformability was evaluated using several biophysical techniques, such as Atomic Force Microscopy. To identify the molecular mechanism induced by α4β1 integrin, and how this would be relevant for T-ALL cell migration, different biochemical and cell biology methods were performed.
Results
We showed that acute lymphoblastic leukemia (ALL) cells cultured on VCAM1 or Fibronectin (ligands of α4β1 integrin) presented higher levels of H3K9me3 than cells in suspension. We confirmed that ALL cells were more sensitive to this effect than normal T-cells. We determined that G9a, a histone methyltransferase, localized at the nuclear envelope and was responsible for H3K9 methylation when T-ALL cells were cultured on VCAM1. We used stable Jurkat cells depleted for G9a to demonstrate that H3K9 methylation contributed to the nuclear stiffness and the ability of ALL cells to migrate in response to chemotaxis and in 2D and 3D environments.
Conclusion
Our results reveal novel functions for G9a in modulating ALL migration, which might contribute to tumor cell dissemination and leukaemia progression.
Session topic: E-poster
Keyword(s): Acute lymphoblastic leukemia, Epigenetic, Integrin, Migration
Abstract: E839
Type: Eposter Presentation
Background
T-Acute Lymphoblastic Leukemia (T-ALL) originates from neoplastic T cell precursors in the thymus. Usually, T-ALL cells have to migrate from the thymus into other tissues, where residual cells might persist after treatments. The nuclear deformability of these tumor cells, and the signals from the cell receptors called integrins are critical to allow cancer cells to squeeze and cross physical barriers. Epigenetics, a novel cancer hallmark that comprises histone modification, histone variants and DNA modifications, leads a new drug generation to prime cancer cells to death. But some epigenetic changes, such as H3K9me3, have been linked with cancer invasion, and might have additional functions leading cancer progression.
Aims
The objective of this study was to explore how epigenetic changes induced by the integrin VLA4/α4β1 control, in a transcriptional independent manner, the nuclear deformability and infiltration of ALL cells.
Methods
Human T (Jurkat) leukemia cell lines, and normal primary T cells were cultured in suspension or on integrin ligands for different times and the levels of H3K9me3 were determined. Nuclear deformability was evaluated using several biophysical techniques, such as Atomic Force Microscopy. To identify the molecular mechanism induced by α4β1 integrin, and how this would be relevant for T-ALL cell migration, different biochemical and cell biology methods were performed.
Results
We showed that acute lymphoblastic leukemia (ALL) cells cultured on VCAM1 or Fibronectin (ligands of α4β1 integrin) presented higher levels of H3K9me3 than cells in suspension. We confirmed that ALL cells were more sensitive to this effect than normal T-cells. We determined that G9a, a histone methyltransferase, localized at the nuclear envelope and was responsible for H3K9 methylation when T-ALL cells were cultured on VCAM1. We used stable Jurkat cells depleted for G9a to demonstrate that H3K9 methylation contributed to the nuclear stiffness and the ability of ALL cells to migrate in response to chemotaxis and in 2D and 3D environments.
Conclusion
Our results reveal novel functions for G9a in modulating ALL migration, which might contribute to tumor cell dissemination and leukaemia progression.
Session topic: E-poster
Keyword(s): Acute lymphoblastic leukemia, Epigenetic, Integrin, Migration
Type: Eposter Presentation
Background
T-Acute Lymphoblastic Leukemia (T-ALL) originates from neoplastic T cell precursors in the thymus. Usually, T-ALL cells have to migrate from the thymus into other tissues, where residual cells might persist after treatments. The nuclear deformability of these tumor cells, and the signals from the cell receptors called integrins are critical to allow cancer cells to squeeze and cross physical barriers. Epigenetics, a novel cancer hallmark that comprises histone modification, histone variants and DNA modifications, leads a new drug generation to prime cancer cells to death. But some epigenetic changes, such as H3K9me3, have been linked with cancer invasion, and might have additional functions leading cancer progression.
Aims
The objective of this study was to explore how epigenetic changes induced by the integrin VLA4/α4β1 control, in a transcriptional independent manner, the nuclear deformability and infiltration of ALL cells.
Methods
Human T (Jurkat) leukemia cell lines, and normal primary T cells were cultured in suspension or on integrin ligands for different times and the levels of H3K9me3 were determined. Nuclear deformability was evaluated using several biophysical techniques, such as Atomic Force Microscopy. To identify the molecular mechanism induced by α4β1 integrin, and how this would be relevant for T-ALL cell migration, different biochemical and cell biology methods were performed.
Results
We showed that acute lymphoblastic leukemia (ALL) cells cultured on VCAM1 or Fibronectin (ligands of α4β1 integrin) presented higher levels of H3K9me3 than cells in suspension. We confirmed that ALL cells were more sensitive to this effect than normal T-cells. We determined that G9a, a histone methyltransferase, localized at the nuclear envelope and was responsible for H3K9 methylation when T-ALL cells were cultured on VCAM1. We used stable Jurkat cells depleted for G9a to demonstrate that H3K9 methylation contributed to the nuclear stiffness and the ability of ALL cells to migrate in response to chemotaxis and in 2D and 3D environments.
Conclusion
Our results reveal novel functions for G9a in modulating ALL migration, which might contribute to tumor cell dissemination and leukaemia progression.
Session topic: E-poster
Keyword(s): Acute lymphoblastic leukemia, Epigenetic, Integrin, Migration
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