Chronic Myelogenous Leukemia
Chronic Myelogenous Leukemia is a disorder characterized by the uncontrolled cell division of a specific white blood cell (WBC) called a myeloid.
DNA Mistakes
Chronic Myelogenous Leukemia (CML) occurs because of a reciprocal translocation. This means that during cell division, two chromosomes swap some of their genes. In the case of CML, chromosomes 9 and 22 swap genes and form a very small chromosome called a Philadelphia chromosome (Ph1).
Effects of the DNA Mistake
When this chromosomes 9 and 22 swap genes, they place them on the Ph1 chromosome and create a gene for a totally new protein. Chromosome 9 usually codes for a tyrosine kinase called ABL. Chromosome 22 usually codes for a protein called BCR. The new oncogene on Ph1, a gene that causes cancer, is responsible for the synthesis of the BCR-ABL tyrosine, a merging of the two proteins that would be made.
BCR-ABL
BCR-ABL functions as a tyrosine kinase in the cytoplasm. However, it produces altered proteins and causes cascades at the wrong time. The cell responds to these proteins and cascades by dividing uncontrollably.
NFkB
NFkB is a kinase that acts as a transcription factor. When it is not needed, high amounts of IkBa can be found in the cytoplasm, which blocks NFkB. When normal cell division needs to occur, a signal will activate proteins that will degrade IkBa, which will allow NFkB to play its part.
In a cancerous cell, BCR-ABL's phosphorylation cascade activates the degradation of IkBa but it never deactivates. With no IkBa, NFkB keeps on transcribing genes for proteins in the immune system, usually WBC.
In a cancerous cell, BCR-ABL's phosphorylation cascade activates the degradation of IkBa but it never deactivates. With no IkBa, NFkB keeps on transcribing genes for proteins in the immune system, usually WBC.
BCR-ABL and the Ras Pathway
BCR-ABL has been found to amplify the signal sent out through the Ras pathway as well as to keep it perpetually activated. The Ras pathways are usually responsible for the expression of certain genes. In this case, the Ras pathway is affected because its structure is mutated, which inhibits its deactivation. Because it is never deactivated, genes be perpetually expressed, causing cancer cells.
BCR-ABL and PI3-K/Akt
The molecule PI3-K/Akt is a lipid kinase that is partially responsible for cell division. BCR-ABL continually over expresses this and the cell keeps dividing.