The c-myb gene functions as a proto-oncogene and a transcription factor. It produces the c-Myb protein, which regulates the activity of other genes. This regulation involves controlling when and how genes are turned on or off, influencing various cellular activities.
The Role of c-myb in Healthy Cells
The c-myb gene is an evolutionarily conserved transcription factor, its function maintained across many species. It is active in rapidly dividing and differentiating cells, especially within the blood-forming system. The c-Myb protein helps control cell growth and specialization.
In the bone marrow, c-myb regulates hematopoiesis, the process of forming all types of blood cells, including red blood cells, white blood cells, and platelets. It influences the proliferation, differentiation, and survival of hematopoietic stem cells and progenitor cells.
Studies in mice show c-myb is necessary for definitive hematopoiesis, the formation of adult blood cells. Without a functional c-myb gene, normal fetal blood cell development is impaired. While its primary role is in blood cell formation, c-myb is also present in other tissues, such as the brain and colon.
c-myb and Cancer Development
When c-myb gene activity is disrupted, it contributes to the development and progression of various cancers. This gene is classified as a proto-oncogene, meaning it can become an oncogene—a gene that promotes cancer—if it undergoes mutations or is overexpressed. Such dysregulation can lead to uncontrolled cell growth and a failure of normal cell death processes.
Overexpression, where too much c-Myb protein is produced, is a common mechanism of c-myb dysregulation. This is observed in several types of leukemia, including acute myeloid leukemia (AML) and T-cell acute lymphoblastic leukemia (ALL). In these cancers, increased c-Myb activity drives the proliferation of cancerous blood cells.
c-myb dysregulation is also linked to certain solid tumors. Overexpression has been noted in some cases of breast and colorectal cancer. In adenoid cystic carcinoma (ACC), fusion proteins involving c-myb and NFIB have been identified, which contribute to tumor growth.
c-myb becomes dysregulated through gene amplification (multiple gene copies) or chromosomal translocations (chromosome rearrangements). These changes result in c-Myb promoting cell cycle progression and inhibiting cell death, fostering tumor development.
Exploring Therapeutic Strategies
Targeting c-myb activity presents a promising area for therapeutic research. Current strategies aim to modulate the c-myb protein or its gene expression to impede cancer cell growth and survival. These approaches are largely in experimental or early clinical stages.
One strategy involves developing small molecule inhibitors. These compounds bind directly to the c-Myb protein, preventing it from interacting with DNA or other proteins necessary for its function. By blocking these interactions, small molecule inhibitors can reduce the expression of genes that c-Myb normally activates, hindering cancer cell proliferation.
Other approaches focus on gene expression at the RNA level. Antisense oligonucleotides are synthetic strands of genetic material that bind to c-myb messenger RNA (mRNA), preventing its translation into the c-Myb protein. Similarly, RNA interference (RNAi) techniques, using small interfering RNAs (siRNAs), can degrade c-myb mRNA, leading to a decrease in c-Myb protein levels within cancer cells.
Research also explores targeting regulatory pathways that influence c-myb activity. For example, disrupting the interaction between c-Myb and coactivator proteins like p300 is being investigated to inhibit its oncogenic function. While these interventions are not yet widely available as treatments, they represent steps in developing new, targeted therapies for c-myb-driven cancers.