Chronic Lymphocytic Leukaemia
Chronic lymphocytic leukaemia is often indolent and, for many patients, is observed rather than treated for a considerable period. When treatment is needed, molecular markers substantially shape the discussion.
Disease categories
Major disease categories
- Chronic lymphocytic leukaemia
- Small lymphocytic lymphoma
- Monoclonal B-cell lymphocytosis
- Richter transformation
Molecular
Molecular considerations
IGHV mutational status, TP53 alteration and del(17p) carry recognised prognostic and predictive weight. del(11q), del(13q) and trisomy 12 form part of standard cytogenetic assessment.
Markers commonly discussed in chronic lymphocytic leukaemia
- IGHV mutational status
- TP53
- del(17p)
- del(11q)
- del(13q)
- Trisomy 12
- β2-microglobulin
Not exhaustive, and not every marker is assessed in every patient. Which of these is relevant depends on the individual case and should be discussed with the treating team.
Testing
Genomic testing considerations
FISH panel and TP53 assessment are discussed before each line of therapy rather than once at diagnosis, because the profile can change.
Germline
Germline considerations
Familial clustering is described; germline assessment is considered where family history is strong.
Molecular monitoring
ctDNA and liquid biopsy considerations
Measurable residual disease assessment in blood and marrow is used in research and increasingly in practice discussion.
Single-cell & computation
Single-cell and algorithmic approaches
Haematological malignancy is where single-cell analysis is most directly applicable, because the tissue is already a cell suspension. Single-cell DNA sequencing resolves whether co-occurring alterations sit in the same clone or in competing clones — a distinction bulk sequencing cannot make and which changes the interpretation substantially. Single-cell RNA analysis characterises differentiation state and microenvironmental interaction. Algorithm work includes measurable residual disease detection at high sensitivity, clonal phylogeny reconstruction across timepoints, and risk models built on combined cytogenetic and molecular features.
Decisions
Treatment decision questions
Questions worth raising with a treating team when a decision is being made:
- Has TP53 and del(17p) status been assessed before starting treatment?
- Is IGHV mutational status known?
- Is treatment actually indicated, or is observation appropriate?
Resistance
Resistance and recurrence questions
- Has TP53 status been repeated, since it can be acquired?
- Has Richter transformation been considered where there is rapid clinical change?
Trials
Clinical trial considerations
TP53 status and prior therapy classes shape eligibility.
When a precision oncology review may help
A review is most useful where the standard pathway has been exhausted or where the picture is more complicated than a protocol accounts for — rare presentations, treatment resistance, complex or apparently contradictory molecular findings, or a decision between several defensible options.
The output is a structured analysis and a set of questions for the treating team. It is not treatment, and it does not replace the treating oncologist.