Genetics

The Role of the Philadelphia Chromosome Translocation in Leukemia



Tweet
Shawn Wells's image for:
"The Role of the Philadelphia Chromosome Translocation in Leukemia"
Caption: 
Location: 
Image by: 
©  

Each year in the United States alone, more than 40,000 adults, and in excess of 3,000 children, are diagnosed with leukemia.  That’s a staggering number of new cases each year.  This cancer, which affects the tissues in bone marrow that form blood, causes an uncontrolled production of abnormal white blood cells.    Normally, healthy white blood cells will die off when they become old or damaged.  However, in leukemia patients, abnormally formed leukemia cells don’t die off as they should, and their proliferation crowds out the healthy blood cells.

Study of this life-threatening disease has discovered a unique chromosome abnormality in certain leukemias such as chronic myeloid leukemia and acute lymphoblastic leukemia.  In these and certain other forms of leukemia there exists a condition in the leukemic cells a translocation between one chromosome 9 and one chromosome 22.  This results in one chromosome 9 being longer than normal, while one chromosome 22 is shorter than normal.  The shorter chromosome 22 is known as the Philadelphia chromosome.  So named because the chromosome was discovered at a hospital in Philadelphia.  This translocation between chromosomes takes place, usually, in only a single bone marrow cell, but then spreads through the process of clonal expansion.

The DNA material that becomes removed from the chromosome 9 to the chromosome 22 contains the proto-oncogene designated c-ABL.  A proto-oncogene is the gene that, when mutated, can contribute to converting a normal cell into a cancer cell.  In this case, leukemic cells.

The c-ABL from chromosome 9 becomes inserted in chromosome 22 next to a gene known as BCR.  The two parts then work together in the mutated chromosome to form a new message, one that is dangerous to the human body.

The mutated chromosome 22, or Philadelphia chromosome, produces an abnormal protein that causes the process of cell production to be carried out all the time, rather than only when a growth factor stimulates such growth, as occurs in healthy non-cancerous cells.  The leukemic cells gradually take up so much room there is little left for the body’s healthy blood cells.  And since the leukemic cells are incapable of doing what white blood cells are supposed to, and the body is able to produce less and less healthy blood cells, the patient may bleed easily and for no apparent reason.  Bleeding from the gums or bruises with no known cause are common.  Infections are also a concern with this type of cancer, with a lack of healthy white blood cells.

Other symptoms include general weakness or being tired, pain in the bones and joints, swollen liver, chronic headaches, vomiting, and seizures.

The treatment for all types of leukemia involves radiation and chemotherapy treatments to kill the patient’s affected bone marrow, and then either using a complete bone marrow transplant or using stem cells from a healthy donor’s bone marrow injected into the patient.  However, more recently there have been some promising medical trials with a drug called Imatinib Mesylate.  It has been approved by the Food and Drug Administration for use in leukemia patients as an alternative to conventional cancer treatments.  The drug fits into the active site of the c-ABL protein, and disrupts the messages that create the unchecked proliferation of the leukemic cells.  In trials, patients who took this drug showed no further progression of the disease.

Tweet
More about this author: Shawn Wells

From Around the Web




ARTICLE SOURCES AND CITATIONS
  • InfoBoxCallToAction ActionArrowhttp://www.cancer.gov/cancertopics/wyntk/leukemia/allpages
  • InfoBoxCallToAction ActionArrowhttp://users.rcn.com/jkimball.ma.ultranet/BiologyPages/C/CML.html
  • InfoBoxCallToAction ActionArrowhttp://www.medterms.com/script/main/art.asp?articlekey=4870
  • InfoBoxCallToAction ActionArrowhttp://users.rcn.com/jkimball.ma.ultranet/BiologyPages/O/Oncogenes.html
  • InfoBoxCallToAction ActionArrowhttp://www.cancer.gov/cancertopics/druginfo/imatinibmesylate