Cause of Chronic Lymphocytic Leukemia (CLL)
The exact cause of CLL remains unknown, with no proven relationship to viruses or specific genes, though there is strong evidence for inherited genetic susceptibility with a 6- to 9-fold increased risk among family members of CLL patients. 1
Genetic Susceptibility
- Family members of CLL patients have a sixfold to ninefold increased risk of developing the disease, indicating a clear inherited genetic component 1
- This familial clustering represents one of the strongest risk factors identified for CLL development 1
- Despite this genetic predisposition, no specific causative genes have been definitively identified 2
Environmental and Epidemiological Factors
- Epidemiological data suggest that both genetic and environmental factors may play a role in CLL development, though specific environmental triggers have not been established 2
- CLL is notably the most common leukemia in Western countries but is rare in Asian populations, suggesting possible geographic or ethnic factors 1
- No relationship with viral infections has been demonstrated, unlike some other hematologic malignancies 2
Pathophysiology of Leukemic Transformation
While not the primary "cause," the disease process involves:
- Specific genomic alterations that impair apoptosis of clonal B-cells, leading to their accumulation rather than normal cell death 3
- These genomic changes interfere with the regulation of both proliferation and apoptosis in clonal B-cells 4
- Common cytogenetic abnormalities include deletions of chromosome 17p (del[17p]), 11q, 13q, and trisomy 12, though these are consequences rather than causes of the disease 1
Important Clinical Context
- The median age at diagnosis is 72 years, with incidence increasing dramatically with age (>30 per 100,000/year in those over 80 years) 1
- Approximately 10% of patients are younger than 55 years at diagnosis 1
- Routine screening for CLL is not recommended either in the general population or in relatives of patients with CLL, despite the increased familial risk 1