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Chronic lymphocytic leukemia is the only type of leukemia that has not been linked with exposure to ionizing radiation, chemicals, or drugs. Although the exact cause of chronic lymphocytic leukemia (CLL) is currently not known, researchers have recently discovered that certain mutations (genetic alterations or errors) that occur in the DNA of normal bone marrow cells can cause these cells to transform into leukemic cells. Deoxyribonucleic acid (DNA) molecules carry the genetic information necessary for the organization and functioning of most living cells and control the inheritance of characteristics. Chromosomes are structures of compact intertwined molecules of DNA found in the nucleus of cells. Chromosomes contain the cell's genetic information. Humans normally have 46 chromosomes.

Cytogenetic studies, special tests that can detect specific genetic mutations of chromosomes, have shown that patients with CLL often have a loss of part of a chromosome. This type of genetic mutation is called a deletion. In patients with CLL, the deletion is most often seen on chromosome 11 or 13. Other chromosomal abnormalities can also be detected in patients with CLL such as an extra chromosome 12 (trisomy 12).