The Philadelphia Chromosome, circa 1960
Less than a decade after Watson and Crick published their landmark paper on the structure of DNA, two Philadelphia researchers noticed that the blood cells of patients with chronic myelogenous leukemia (CML) had an unusually tiny chromosome. At a time when the genetic underpinnings of disease were unclear, the discovery of this abnormality—dubbed the Philadelphia Chromosome—marked the first time a specific genetic defect was linked to a cancer, paving the way for drugs that targeted the defect and turned this rare leukemia into a manageable disease.
1 - In 1956, Peter Nowell joined the University of Pennsylvania faculty and began what he calls “poorly defined studies of leukemia.” By rinsing blood cells with tap water before staining and mounting them on a microscope slide, Nowell inadvertently caused the cells to swell and flatten, and most importantly, disrupted their mitotic spindle—allowing him to visualize their chromosomes more easily.
2 - Nowell teamed up with David Hungerford, a PhD student at the nearby Fox Chase Cancer Center, and together they detected that a chunk seemed to be missing from chromosome 22 in the leukocytes of CML patients. They published their findings in 1960, and the shortened chromosome was named after the city where it was discovered. But their suggestion that the aberration itself was causing the cells to proliferate abnormally met with a less-than-enthusiastic reception, recalls Nowell. One reviewer even said that the observation probably had no relevance to the clinical disease.
3 - A decade later, geneticist Janet Rowley of the University of Chicago showed that the Philadelphia Chromosome resulted from a swap between the ends of chromosome 22 and chromosome 9. Scientists subsequently demonstrated that this translocation resulted in the production of a mutant protein that did indeed incite cells to grow uncontrollably.
In 2001, Novartis introduced a new drug known as Gleevec, which directly inhibits the abnormal protein and halts the production of cancerous white blood cells in the bone marrow. With the introduction of Gleevec and its derivatives, survival rates of CML patients rose from 30 percent to nearly 90 percent. “This is one of the few human cancers where we have a very high rate of cure,” Nowell says.
Read more: The Philadelphia Chromosome, circa 1960 - The Scientist - Magazine of the Life Sciences http://www.the-scientist.com/article/display/57846/#ixzz17xGwMTR2
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