Philadelphia chromosome
Meaning of Philadelphia chromosome: The first chromosome fault ever tied to a specific cancer, and now the target of drugs that switch off the protein it creates.
Definition of Philadelphia chromosome
The Philadelphia chromosome is a shortened chromosome 22 produced when segments of chromosomes 9 and 22 swap places. The exchange joins two genes, BCR and ABL1, into one fused gene whose protein is stuck permanently in the on position. That protein drives blood-forming cells to multiply without restraint, and it is present in almost every case of chronic myeloid leukemia.
How does the swap happen?
Each chromosome is a single long strand of DNA. Occasionally two strands break and are rejoined to the wrong partner, an event called a translocation. Here chromosome 9 and chromosome 22 exchange tips. Chromosome 22 ends up shorter than normal, and that stunted chromosome is what shows under a microscope. The fault arises inside a single cell in the bone marrow during life. It is not inherited, and it is not passed to children.
Why does the fused gene cause disease?
The ABL1 gene normally makes an enzyme that passes on growth signals only when instructed. Fusing it to BCR removes the off switch, so the enzyme signals constantly. White cell precursors read that as a permanent order to divide, and they also survive longer than they should. The marrow fills with maturing white cells, the spleen enlarges as it takes up the overflow, and the white cell count in the blood climbs.
Which diseases carry it?
| Disease | How often the change is present |
|---|---|
| Chronic myeloid leukemia | Almost every case; the diagnosis depends on it |
| Acute lymphoblastic leukemia | A minority, more often in adults than children |
| Acute myeloid leukemia | Rare |
Why does it matter for treatment?
Because the disease depends on one overactive enzyme, a drug shaped to plug that enzyme can shut the process down. Tyrosine kinase inhibitors, beginning with imatinib, do exactly that, and their arrival changed chronic myeloid leukemia from a disease measured in a few years into one many people live with long term. The same fused gene doubles as a monitoring tool: laboratories can count copies of its message in a blood sample and follow the response over time, at a sensitivity far beyond what a microscope offers.
Also known as
Used in a sentence
Cytogenetic analysis of the marrow confirmed the presence of the Philadelphia chromosome.
Good to know
The Philadelphia chromosome is acquired by a blood-forming cell during life rather than inherited, so it does not pass to a person's children.