'Til Death Do Them Part

This stuff is complicated and I am trying to learn what it means!

The eye of my cat, Timmy
What is the Philadelphia Chromosome and what does it have to do with me?

The chromosome abnormality that causes chronic myeloid leukemia (CML). Abbreviated as the Ph chromosome. I have this in my bone marrow. It is not normal to have it.

The Ph chromosome is an abnormally short chromosome 22 that is one of the two chromosomes involved in a translocation (an exchange of material) with chromosome 9.

To the best of my understanding chromosome 22 has divorced it's partner and is now marrying chromosome 9. They cannot get divorced. They will reside in my body until I die.

This translocation takes place in a single bone marrow cell and, through the process of the production of many cells from this one mutant cell, it gives rise to the leukemia.

The discovery in Philadelphia in 1960 of the Ph chromosome was a landmark. It was the first consistent chromosome abnormality found in any kind of malignancy. Now other cancers are being identified genetically.

The discovery led to the identification in CML cells of the BCR-ABL fusion gene and its corresponding protein. ABL and BCR are normal genes on chromosomes 9 and 22, respectively. 

The ABL gene encodes a tyrosine kinase enzyme whose activity is tightly regulated (controlled). In the formation of the Ph translocation, two fusion genes are generated: BCR-ABL on the Ph chromosome and ABL-BCR on the chromosome 9 participating in the translocation. 

The BCR-ABL gene encodes a protein with deregulated (uncontrolled) tyrosine kinase activity. The presence of this protein in the CML cells is strong evidence of its pathogenetic (disease-causing) role. 

The efficacy in CML of a drug that inhibits the BCR-ABL tyrosine kinase has provided the final proof that the BCR-ABL oncoprotein is the unique cause of CML.

The Ph chromosome is also found in a form of acute lymphoblastic leukemia (ALL). It seems highly probable that this form of ALL is due to the same chromosomal and molecular mechanisms as CML.

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