Chronic lymphocytic leukemia

It is one of the most common hematologic malignancies, and is characterized by the presence of uncontrolled proliferation of B lymphocytes. It is the most frequent subtype of leukemia in adults in Western countries with an average incidence of 12 cases per 100,000 individuals per year, which increases exponentially with age and with a highly variable prognosis.

The exact causes that initiate the process of uncontrolled B-lymphocyte proliferation are unknown. Studies have identified important chromosomal changes in the development of CLL, but it is not yet clear which genes are involved or exactly how they lead to leukemia. It has also been noted that the DNA changes associated with CLL usually occur throughout a person's life, rather than being passed on from the parents (inherited). However, the following have been described as factors that may increase the risk of CLL:

  • The disease mainly affects older adults, usually from the age of 60 years onwards.
  • It is slightly more common in men than in women.
  • People of Caucasian ancestry are more likely to develop chronic lymphocytic leukemia than others such as Asians.
  • Exposure to chemicals such as herbicides (agent orange) and insecticides or pesticides have been associated with increased risk.
  • Monoclonal B-cell lymphocytosis causes an increase in the number of B-cells, which may favor the development of chronic lymphocytic leukemia.

Research has revealed a strong genetic component to CLL with an 8-fold increased risk in relatives of patients. In addition, no consistent and reproducible environmental risk factor has been identified to date, although elevated body mass index and smoking appear to be the main contributors to associated mortality and disability. Given the relevant genetic contribution, the GWAS study, conducted on more than 6200 cases and 17500 controls, has provided a more complete picture of the predisposition to CLL by identifying 35 major risk factors for CLL.Given the relevant genetic contribution, the GWAS study, conducted on more than 6200 cases and 17500 controls, has provided a more complete picture of CLL predisposition by identifying 35 loci involved in cellular pathways critical for B-cell development, especially B-cell receptor (BCR)-mediated signaling.


More than 80% of patients with CLL have no symptoms and CLL is diagnosed by a routine blood test or by chance. In the rest of the cases, the main symptoms may be:

  • Asthenia, fatigue, weight loss.
  • Adenopathy or enlarged lymph nodes.
  • Repeated infections.

Occasionally the spleen (splenomegaly) or liver (hepatomegaly) may be enlarged and may cause abdominal discomfort. Unlike in other blood neoplasms, fever, night sweats and weight loss are rare.


There are very few known risk factors for chronic lymphocytic leukemia, and most of them cannot be avoided, beyond having first-degree relatives.

Number of observed variants

13.5 million variants

Number of risk loci analyzed in the study

36 loci


The American Cancer Society. Chronic Lymphocytic Leukaemia [April 2022]

Josep Carreras Leukaemia Foundation [April 2022]

Mayo Clinic [April 2022]

Law PJ et al. Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukemia. Nature Communications. 2017 Feb; 8:14175.

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