Medical Definition of Philadelphia chromosome (Ph)

Reviewed on 6/3/2021

Philadelphia chromosome (Ph): The chromosome abnormality that causes chronic myeloid leukemia (CML). Abbreviated as the Ph chromosome.

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. This translocation takes place in a single bone marrow cell and, through the process of clonal expansion (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. 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.

Philadelphia chromosome is the hallmark of chronic myeloid leukemia (CML). The Philadelphia (Ph) chromosome is an abbreviated chromosome 22 that was shortchanged in a reciprocal exchange of material with chromosome 9. This translocation occurs in a cell in the bone-marrow, and causes CML It is also found in a form of acute lymphoblastic leukemia (ALL). On a molecular level the Philadelphia chromosome translocation results in the production of a fusion protein. A large portion of a proto-oncogene, called ABL, on chromosome 9 is translocated to the BCR gene on chromosome 22. The two gene segments are fused and ultimately produce a chimeric protein that is larger than the normal ABL protein. The malignant state is a consequence of this process. Understanding this process led to the development of the drug imatinib mesylate (Gleevec) the first in a new class of genetically targeted agents, a major advance in cancer treatment..



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