The Philadelphia chromosome has an important role in chronic myeloid leukemia (CML). It's found in the leukemia cells of nearly all CML patients. So it follows that if you want to understand the origins of what's called Philadelphia chromosome-positive CML (often written Ph+ CML), you'll want to know more about the Philadelphia chromosome itself. Starting with—why Philadelphia, and what makes the chromosome
Who found the chromosome?
The Philadelphia chromosome was first identified and described in 1960 by 2 Philadelphia researchers,
Dr. Peter Nowell of the University of Pennsylvania School of Medicine and the late David Hungerford of Fox Chase Cancer Center's Institute for Cancer Research. The real story is that in discovering the Philadelphia chromosome they were the first to uncover a gene-based cause for leukemia. The Philadelphia chromosome is the result of a genetic alteration. Studying this abnormal chromosome eventually led to the formulation of cancer drugs that worked by targeting the gene itself.
And by the way, what is a chromosome?
Before getting into the specifics of the Philadelphia chromosome, you may want to know a little more about chromosomes in general.
Chromosomes are complex structures in the cell nucleus housing deoxyribonucleic acid (DNA) and special proteins. Individual chromosomes come in pairs of what are called "homologous" chromosomes: meaning twin pairs with the same basic structure, one from the mother and one from the father. Both men and women have 23 pairs each, numbered from 1 to 22, plus 1 X and 1 Y chromosome in men, and 2 X chromosomes
The Philadelphia chromosome is the result of pieces of 2 different chromosomes (numbers 9 and 22) breaking off and changing places. Specifically, part of chromosome #9 breaks away and attaches itself to chromosome #22, while part of #22 attaches itself to #9. This is known as a translocation.
After the switch, the chromosomes are technically still numbered 9 and 22. But they no longer look the same or behave the same. One of the changed chromosomes (#22) is called the Philadelphia chromosome. It's the distinctive way this chromosome acts after the switch that leads to CML.
From a rogue chromosome to rogue cells
After the translocation, the bone marrow makes an enzyme that causes an overabundance of stem cells to develop into white blood cells. You may be thinking that white blood cells are good, because they fight infection. Generally that's true, but these white blood cells don't mature normally. They stay permanently immature, what are called blasts. They multiply when they shouldn't and live longer than they should. They build up in blood and bone marrow leaving less room for healthy white blood cells, red blood cells, and platelets. These cells can also enter the bloodstream, where they can spread to and negatively affect
Genetic. But not inherited.
Two good things about the Philadelphia chromosome. It's not inherited. (Nor is CML.) And several of today's medicines have the express purpose of interfering with its behavior, changing this Philadelphia story in ways no one would have believed in the past.