Lack of interferon consensus sequence binding protein (ICSBP) transcripts in human myeloid leukemias

Area of Science:

• Molecular Biology
• Hematology
• Oncology

Background:

• Interferon consensus sequence binding protein (ICSBP) is an interferon regulatory factor (IRF) family member.
• ICSBP regulates interferon-dependent gene expression via DNA binding.
• ICSBP deficiency in mice causes hematologic alterations resembling chronic myelogenous leukemia (CML).

Purpose of the Study:

• To investigate the role of ICSBP in human myeloid leukemias.
• To determine ICSBP-mRNA expression levels in CML and acute myeloid leukemia (AML) patients.
• To assess the inducibility of ICSBP in leukemic cells.

Main Methods:

• Quantitative analysis of ICSBP-mRNA in patient samples (CML, AML, normal volunteers).
• Analysis of ICSBP expression in sorted B cells.
• Ex vivo induction of ICSBP using interferon-gamma (IFN-gamma).
• In vivo analysis of ICSBP during interferon-alpha (IFN-alpha) treatment.
• Stable transfection of K-562 cell line with ICSBP.

Main Results:

• ICSBP-mRNA expression is significantly impaired in CML (79%) and AML (66%) patients compared to normal volunteers (6%).
• ICSBP deficiency was observed in sorted B cells from CML patients.
• Ex vivo IFN-gamma treatment induced ICSBP transcripts in primary CML cells.
• In vivo IFN-alpha treatment induced ICSBP-mRNA in most CML patients, but levels decreased with disease progression.
• Stable ICSBP transfection did not alter bcr-abl expression in vitro, but an inverse correlation was noted in vivo in some patients.

Conclusions:

• Reduced ICSBP expression is a common feature of human myeloid leukemias.
• ICSBP deficiency may contribute to myeloid leukemogenesis.
• ICSBP is inducible in leukemic cells, suggesting potential therapeutic strategies.