No etiologic factors have been clearly defined for chronic lymphocytic leukemia, although few studies have been performed. Most chronic lymphocytic leukemia cases occur sporadically, but approximately 1 in 20 patients has a familial form of the disease. The presence of familial cases clearly suggests that inherited genetic factors contribute to the development of the disease, although the specific abnormal genes connected to chronic lymphocytic leukemia have not yet been identified. The incidence of chronic lymphocytic leukemia in first-degree relatives is three times greater than in the general population (3 in 10,000, compared with 1 in 10,000).
TABLE.Common Cytogenetic Changes in Chronic Lymphocytic Leukemia and Their Significance
| Marker (Mutation) | Frequencyof Marker
(96) |
Significance of Mutation and Additional Comments |
| Deletions in chromosome 13 | 35-55 | Associated with benign disease (stable or slowly progressing); patients with this marker survive as long as age-matched controls. |
| Additional chromosome 12 | 15-20 | Associated with atypical morphology, aggressive disease, and poor prognosis; patients tend to have unmutated immunoglobulinvariable genes. |
| Deletions in chromosome 11 | 15-20 | Patients have more aggressive disease; patients who are carriers of the ATM genes found on chromosome 11 may be at greater risk of developing chronic lymphocytic leukemia. |
| Defects in chromosome 17 affecting the p53 oncogene | 15 | Associated with advanced disease, high proliferation rate, shortened survival, resistance to chemotherapy, and increased likelihood of Richter’s syndrome. |
ATM = Ataxia-telangiectasia mutated.
Chronic lymphocytic leukemia is less common in the Japanese and other Asian populations than in populations originating in the Western world, and the incidence does not increase in Asian expatriates.
Environmental factors such as ionizing radiation, chemicals, and viruses do not seem to be associated with the pathogenesis of this disease.
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