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Updated: Jul 1, 2026
10:49
Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia
Published on: September 18, 2013
ICER expression inhibits leukemia phenotype and controls tumor progression
1Department of Pediatrics, Laboratory of Oncohematology, University of Padova, Padova, Italy. martina.pigazzi@unipd.it
Leukemia
|September 12, 2008
Summary
Restoring inducible cyclic AMP (cAMP) early repressor (ICER) expression suppresses leukemia progression by reducing CREB protein levels and inhibiting tumor growth. This suggests ICER acts as a tumor suppressor in leukemia.
Area of Science:
- Molecular Biology
- Cancer Research
- Signal Transduction
Background:
- CREB is upregulated in childhood leukemia, promoting disease progression.
- ICER, a repressor of CREB, is downregulated in leukemia.
- The role of restored ICER expression in leukemia is under investigation.
Purpose of the Study:
- To investigate the function of restored ICER expression in leukemia.
- To determine ICER's effects on CREB levels, clonogenic potential, and tumor invasion.
- To elucidate the molecular mechanisms underlying ICER's tumor suppressor activity.
Main Methods:
- Exogenous expression of ICER in leukemia cell lines.
- Assessment of CREB protein levels and clonogenic potential in vitro.
- Evaluation of tumor invasion and bone marrow angiogenesis in vivo using mouse models.
- Analysis of ICER's target genes and promoter binding activity.
Main Results:
- Exogenous ICER expression decreased CREB protein levels and reduced clonogenic potential.
- ICER suppressed HL60 cell invasion and bone marrow angiogenesis in vivo.
- ICER repressed CREB-upregulated target genes, restoring normal cellular pathway regulation.
- ICER is degraded by active ERK, suggesting a mechanism for its downregulation.
Conclusions:
- ICER functions as a tumor suppressor in leukemia.
- Downregulation of ICER in leukemia preserves CREB overexpression, promoting blast proliferation.
- Imbalanced CREB/ICER expression is a pathogenetic feature in leukemogenesis.
- Understanding the CREB/ICER pathway may lead to novel therapeutic strategies for leukemia.
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