Chapter 9: DNA: The Molecule of HeredityIssues in Biology |
Estimated time: 10 minutes
Chapter Section: Chapter 9, Case Study
Long before it was known that the DNA of chromosomes carries the genetic code, scientists had been studying chromosome structure in a variety of organisms. In the early 1900s, Boveri, a French scientist, examined chromosome structure in malignant cells derived from tumors. He, and others, noted that the chromosomes in these cells had two copies of several different chromosomes, had fragmented chromosomes, or had chromosomes with abnormal sizes or shapes. Boveri proposed that the presence of chromosome abnormalities might actually cause the cancer.
In 1960, Peter Nowell and David Hungerford, two researchers in Philadelphia, provided the first indication that Boveri was correct. These scientists were studying the chromosomes of people with a type of leukemia called chronic myelogenous leukemia. This disease primarily affects adults and is characterized by the production of excess numbers of white blood cells known as granulocytes. In a one-paragraph report in the journal, Science, Nowell and Hungerford reported that all seven individuals they were examining had an unusually short chromosome 22. Echoing Boveri's earlier proposal, they hypothesized that the presence of this odd chromosome might be causing the cancer. They turned out to be right, at least partially, as you will see.
Because Nowell and Hungerford worked in Philadelphia, this tiny chromosome 22 came to be called the Philadelphia chromosome by other researchers who began to investigate the possible link between this chromosome and the development of leukemia. On the basis of improved chromosome staining techniques, other researchers discovered that, in people with a Philadelphia chromosome, a portion of chromosome 22 had broken off and was joined to chromosome 9. Over many years of research by laboratories, it was found that the fusion between parts of chromosomes 9 and 22 creates a defective gene: Instead of quietly dying at the proper time, cells with this defect are unable to undergo the normal program of cell "suicide" that operates to regulate the levels of white blood cells. This observation was one of the first in which it was shown that cancers are diseases caused by defective genes. So, how is it that Nowell and Hungerford were only partly right about the Philadelphia chromosome causing cancer? Although the defect that results from the Philadelphia chromosome is important for developing chronic myelogenous leukemia, there are apparently other, as yet unknown genetic changes that must also happen for the disease to progress.
Researchers and physicians continue to study the Philadelphia chromosome to understand the molecular events involved in initiating a cancer. In addition, physicians around the world use the presence of the Philadelphia chromosome to diagnose chronic granulocytic leukemia and to monitor the effectiveness of treatments. For example, if a person is feeling exhausted, lacks an appetite, and has night sweats, the doctor will probably order a blood test to check a variety of things, including the numbers of red and white blood cells. If the presence of excess or immature white blood cells is seen, additional tests, such as bone marrow biopsies, may be performed to look for the presence of the Philadelphia chromosome. If that chromosome is present, the patient is diagnosed with chronic granulocytic leukemia and proper treatment can begin. In many cases, the best option for treatment is a bone marrow transplant. Following the transplant, physicians will continue to monitor the patient’s blood for cells that contain the Philadelphia chromosome. When cells containing this chromosome are no longer present, the patient is considered cured.