Tuesday, June 10, 2008

More about BCR-ABL

In case you are curious about what the BCR-ABL is, I am including some text from the Leukemia and Lymphoma Society that explains some of the information about what it is.

Studies established that two chromosomes, usually chromosomes number 9 and 22, were abnormal [in CML patients]. Pieces of the chromosomes, which are broken off in the leukemic cells of patients with CML, switch with each other. The detached portion of chromosome 9 sticks to the broken end of chromosome 22, and the detached portion of chromosome 22 sticks to the broken end of chromosome 9. This abnormal exchange of parts of chromosomes is called a translocation. This translocation of chromosome pieces occurs only in the damaged stem cell and in the various blood cells derived from that stem cell. The chromosomes of the cells in other tissues are normal.

The breakage on chromosome 9 disrupts a gene referred to as “ABL” (for Abelson, the scientist who first described this gene). The breakage on chromosome 22 involves a gene referred to as “BCR” (for breakpoint cluster region). The human ABL gene is mutated by the breakage of chromosome 9. The mutated gene is translocated to chromosome 22 and fuses with the remaining part of the BCR gene. This fusion between BCR and ABL leads to an abnormal fused gene, called “BCR-ABL.”

The function of a gene is to direct the production of a protein in the cell. In CML, the ABL gene fuses to the BCR gene, resulting in the production of an elongated enzyme protein called “tyrosine kinase.” This elongated protein functions abnormally and leads to dysfunctional regulation of cell growth and survival. The abnormal protein resulting from the mutant BCR-ABL gene is responsible for the development of the disease.

The cause of the chromosomal breakage, occurring in nearly all CML patients, is not known, for the most part. However, in a small number of patients, exposure to very high doses of radiation causes the breakage. This effect has been most carefully studied in the Japanese survivors of the atomic bomb, whose future risk of developing leukemia was significantly increased. A slight increase in risk also occurs in some individuals treated with high-dose radiotherapy for other cancers, such as lymphoma. Exposures to diagnostic dental or medical x-rays have not been associated with an increased risk of CML.

The complete document can be found online at http://www.leukemia-lymphoma.org/attachments/National/br_1173816394.pdf

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