Cancer Dictionary · Blood and lymphatic

Chronic Lymphocytic Leukaemia

Chronic lymphocytic leukaemia is frequently diagnosed incidentally and may be observed for years without treatment. When treatment is needed, TP53 status, del(17p) and IGHV mutational status shape the discussion. TP53 status must be reassessed before each line of treatment, because it can change.

Also called CLL, Small lymphocytic lymphoma, SLL.

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The governing idea

CLL often needs no treatment for years, so the first decision is usually whether to treat at all, and the molecular tests that matter are the ones repeated before each treatment rather than done once at diagnosis.

01Before any molecular question

How it usually presents

Usually established first: confirmation by flow cytometry, clinical stage, and whether there are indications for treatment. Many patients are diagnosed on a routine blood count and never need treatment at all, which makes clear communication about observation particularly important.

Usually already established

Flow cytometry confirmation
Clinical stage
Whether treatment indications are met
TP53 and IGHV status where treatment is being considered

Major disease categories

The divisions below are not labels. Each one changes what the treatment discussion is actually about.

Early-stage, asymptomatic disease

Observation is standard. Treating early has not been shown to help.

Disease meeting treatment indications

Where symptoms, cytopenias or progressive disease prompt treatment.

TP53-aberrant disease

Defined by del(17p) or TP53 mutation. A distinct treatment discussion.

IGHV-unmutated disease

Associated with a different disease course from mutated disease.

Richter transformation

Transformation to an aggressive lymphoma. A distinct and serious event requiring biopsy to confirm.

03What is discussed

Molecular considerations

TP53 mutation and del(17p) together define TP53-aberrant disease and are the most consequential findings. IGHV mutational status is established once and does not change, unlike TP53 status. del(11q), del(13q) and trisomy 12 carry prognostic information. NOTCH1, SF3B1 and BIRC3 alterations are also discussed. At resistance to targeted agents, BTK and PLCG2 mutations and BCL2 mutations are recognised mechanisms.

Biomarkers commonly discussed

TP53 and del(17p)

The most consequential findings, and they must be reassessed before each line of treatment.

IGHV mutational status

Established once, does not change. Distinguishes two different disease courses.

del(11q), del(13q), trisomy 12

Cytogenetic findings carrying prognostic information.

NOTCH1, SF3B1

Additional prognostic alterations.

BTK and PLCG2

Resistance mutations to a specific targeted class.

BCL2

Resistance mutations to a different targeted class.

This is not an exhaustive list, and which markers are relevant depends on the individual case. Not every marker listed is assessed in every patient.

04What is tested, and from what

Testing, inherited risk and blood-based monitoring

Genomic testing considerations

The critical practical point is that TP53 mutation and del(17p) testing must be repeated before each new line of treatment, because clones carrying these alterations can emerge under treatment pressure. IGHV status is established once. Testing at diagnosis in a patient who will be observed is often not necessary, and testing at the point treatment is being considered is what actually matters.

Germline considerations

Familial clustering of CLL is described, and first-degree relatives have a modestly increased risk, but no single high-penetrance gene explains most cases. Formal germline testing is not part of the routine pathway.

Cancer genetics and hereditary risk

ctDNA and liquid biopsy considerations

Blood is the direct sample in CLL, so molecular testing is straightforward. Measurable residual disease assessment after treatment is established and is increasingly used to guide treatment duration in some approaches.

When molecular information matters

Testing that arrives after the decision it was meant to inform has already been made is a common and avoidable problem. This is the sequence in which molecular information tends to become relevant.

At diagnosisConfirmation and staging. Many patients need no treatment, and explaining observation clearly matters.
When treatment indications are metThis is when TP53 and IGHV testing matter, not necessarily at diagnosis.
Before every subsequent lineTP53 status must be repeated, because it can change under treatment pressure.
Where there is rapid clinical changeRichter transformation should be considered and confirmed by biopsy rather than assumed.

06Take these to your team

Questions worth raising

When a decision is being made

Questions worth raising with a treating team.

Are treatment indications actually met, or is observation still appropriate?
Has TP53 mutation and del(17p) testing been done before this line of treatment, rather than relying on a result from diagnosis?
Has IGHV status been established, recognising that it does not need repeating?
Has the reasoning for observation been explained clearly, since being told to wait can be harder than being treated?

At progression, recurrence or resistance

The molecular picture at diagnosis is not always the molecular picture later.

Has TP53 status been repeated, since new clones can emerge under treatment?
Where a targeted agent has stopped working, has resistance mutation testing been considered?
Where there is rapid clinical deterioration, has Richter transformation been excluded by biopsy?

07What shapes eligibility

Clinical trial considerations

Eligibility is written around TP53 status, prior therapy classes and measurable residual disease. Because CLL treatment now spans several distinct targeted classes, the specific prior agents matter more than the number of prior lines.

Ask about trial matching

Plain-language glossary for this entry (4 terms)

Term	What it means
Watch and wait	Observing without treating. Standard in early asymptomatic CLL, and not a failure to act.
IGHV mutational status	Whether the immunoglobulin gene has undergone normal mutation. Distinguishes two disease courses.
del(17p)	Loss of part of chromosome 17, where TP53 sits. A consequential finding.
Richter transformation	Change into an aggressive lymphoma. Requires biopsy to confirm.

Where OnKommon fits

These are the services most often relevant to this cancer. Which of them applies is a clinical question, not an automatic one.

Signature B ALLProfiling for lymphoblastic leukaemia.See how it works SentinelSerial monitoring during active treatment.See how it works Blueprint CareThe decision report that reads the profile and ranks the options.See how it works

This entry is educational. It describes what is commonly discussed in this cancer, not what should happen for any individual. Which of it applies depends on the specific diagnosis, stage, prior treatment and the person themselves. Nothing here is a recommendation, and no list of biomarkers here is exhaustive. Decisions belong with a treating team who know the whole case.

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