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Updated: Aug 12, 2026
Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia
Published on: September 18, 2013
Dual effect of targeting LSD1 on the invasiveness and the mechanical response of acute lymphoblastic leukemia cells
Raquel González-Novo1, Marina Armesto1, África González-Murillo2
1Department of Molecular Medicine, Centro de Investigaciones Biológicas Margarita Salas (CIB Margarita Salas-CSIC), Madrid, Spain.
Abstract:
Epigenetic alterations are hallmarks of cancer, with histone modifiers playing critical roles in gene transcription, DNA homeostasis, and other nuclear functions. Lysine-specific demethylase 1 (LSD1), a key regulator of H3K4 methylation, has emerged as a promising pharmacological target in cancer treatment, including leukemia. Acute lymphoblastic leukemia (ALL), the most common pediatric cancer, remains a significant therapeutic challenge due to limited understanding of how epigenetic therapy impacts leukemia dissemination. In this study, we demonstrate that targeting LSD1 enhances the invasive capacity of ALL cells, inducing an elongated, invasive phenotype and increasing nuclear deformability. Using a 3D matrix model, LSD1 inhibition promoted ALL cell invasion without significantly affecting the cell cycle progression or apoptosis under the tested conditions. Interestingly, LSD1 targeting reduced ALL cell spreading and tissue colonization in vivo, suggesting differential effects depending on the cellular context. Our findings indicate that LSD1 inhibition impairs chemotactic responses and transendothelial migration, key processes for extravasation and in vivo invasiveness. These results reveal a dual role for LSD1 in leukemia cell migration: promoting invasiveness in 3D environments while reducing extravasation and chemotaxis in vivo. This dual effect underscores the importance of cellular context in determining therapeutic outcomes and the development of strategies targeting specific stages of leukemia dissemination.
Insights
Targeting Lysine-specific demethylase 1 (LSD1) in acute lymphoblastic leukemia (ALL) has a dual effect. While enhancing invasion in 3D models, it impairs leukemia cell migration and colonization in vivo.
Area of Science:
- Cancer epigenetics
- Molecular oncology
- Leukemia research
Background:
- Epigenetic alterations, particularly histone modifications, are crucial in cancer development.
- Lysine-specific demethylase 1 (LSD1) is a key epigenetic regulator and a potential therapeutic target in leukemia.
- Understanding epigenetic therapy's impact on acute lymphoblastic leukemia (ALL) dissemination is vital for treatment.
Purpose of the Study:
- To investigate the role of LSD1 inhibition in ALL cell invasion and dissemination.
- To elucidate the context-dependent effects of LSD1 targeting on leukemia cell migration.
Main Methods:
- Utilized 3D matrix models to assess ALL cell invasion and nuclear deformability upon LSD1 inhibition.
- Evaluated cell cycle progression and apoptosis under LSD1 targeting conditions.
- Assessed in vivo ALL cell spreading, tissue colonization, chemotaxis, and transendothelial migration.
Main Results:
- LSD1 inhibition enhanced ALL cell invasiveness and nuclear deformability in 3D models.
- LSD1 targeting did not significantly alter cell cycle or apoptosis in tested conditions.
- In vivo, LSD1 inhibition reduced ALL cell spreading, tissue colonization, chemotaxis, and transendothelial migration.
Conclusions:
- LSD1 inhibition exhibits a dual role in leukemia cell migration, promoting invasion in 3D environments but impairing extravasation and chemotaxis in vivo.
- The cellular context significantly influences the therapeutic outcomes of LSD1 targeting in leukemia.
- Findings highlight the complexity of targeting epigenetic modifiers for leukemia dissemination strategies.
