v-abl activates embryonic globin gene expression in mouse erythroleukemia cells

Area of Science:

• Molecular Biology
• Oncology
• Genetics

Background:

• The Philadelphia chromosome (Ph) translocation is a hallmark of chronic myelogenous leukemia (CML), present in 90-95% of patients.
• This translocation involves the c-abl protooncogene and is associated with altered gene expression, including embryonic globin genes in K562 CML cells.

Purpose of the Study:

• To investigate whether the protein product of the translocated c-abl protooncogene directly activates embryonic globin gene expression.
• To elucidate the role of the c-abl protooncogene in the pathogenesis of CML.

Main Methods:

• Transfection of the v-abl oncogene, which shares autophosphorylation properties with the translocated c-abl protooncogene, into mouse erythroleukemia cells.
• Analysis of embryonic globin gene expression in v-abl-transfected cells.

Main Results:

• Mouse erythroleukemia cells containing multiple copies of the v-abl transgenome showed activation of mouse embryonic globin gene expression.
• This activation demonstrates a functional link between v-abl oncogene expression and embryonic globin gene regulation.

Conclusions:

• The translocated c-abl protooncogene is central to the pathogenesis of chronic myelogenous leukemia.
• The c-abl protooncogene may mediate the activation of embryonic globin genes in certain CML cell lines.