The exact cause for CLL is unknown. However, in most cases abnormalities in patients’ chromosomes or genes can be found.
Chromosome and gene abnormalities involved in CLL, and their implication for prognosis are shown in Table 3.
Table 3 Cytogenetic abnormality in CLL and implication for prognosis
| Chromosomal abnormality | Prognosis | Incidence (% of patients) |
| 17p13 and TP53 deletion* | Poor | 30% |
| 17p13 deletion alone | Poor | 5-8% |
| TP53 gene deletion/mutation alone | Poor | 4-5% |
| 13q14 deletion | Good | 55% |
| 11q23 deletion | Poor | 18% |
| 12q trisomy (3 copies of chromosome 12q) | Intermediate | 16% |
| Unmutated IgVH genes | Poor | 44% |
| Mutated IgVH genes | Good | 55% |
* A chromosome deletion is when part, or the whole chromosome, is deleted
- In patients with CLL, cytogenetic analysis has detected several recurrent genetic anomalies that greatly affects the way CLL behaves and how patients respond to treatment.
- Cytogenetics is the branch of genetics that studies the structure of DNA within the cell nucleus.
- There are three important mutations in the leukaemia cells of patients which indicate how the CLL develops and how patients respond to treatment. These are:
- Deletion of chromosome 17p (del17p):
- Present in up to 10% of CLL patients
- Consist of a deletion of part of the chromosome called 17p
- This abnormality can make some treatments for CLL less effective.
- TP53 gene mutation:
- Present in 4-5% of CLL patients
- The TP53 gene helps stop the growth of tumours
- Mutation in the TP53 gene makes CLL less responsive to some treatments.
- Immunoglobulin heavy chain variable (IGHV) gene mutations:
- Present in 55% of patients (Gadhia et al 2019)
- Mutations of IGHV genes in the B-cell receptor inhibitors (BCRs)
- BCRs are proteins on the outside of B-cells
- Patients with mutations of IGHV genes show a better response to treatment than people without IGHVregion mutations.
