Haematological Malignancies
Haematological malignancies are defined molecularly to a greater degree than most solid tumours. Cytogenetic and molecular findings do not supplement the diagnosis; in many entities they constitute it.
Disease categories
Major disease categories
- Acute leukaemias
- Chronic leukaemias
- Lymphomas
- Multiple myeloma and plasma cell disorders
- Myelodysplastic syndromes
- Myeloproliferative neoplasms
Molecular
Molecular considerations
Entity-defining findings include BCR::ABL1 in chronic myeloid leukaemia, recurrent cytogenetic abnormalities in acute myeloid leukaemia, JAK2, CALR and MPL in myeloproliferative neoplasms, and defining rearrangements across the lymphomas.
Markers commonly discussed in haematological malignancies
- BCR::ABL1
- JAK2 / CALR / MPL
- FLT3
- NPM1
- TP53
- IGHV
- del(17p)
- MRD
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
Cytogenetics, fluorescence in situ hybridisation, immunophenotyping and molecular panels are integral to diagnosis and monitoring.
Germline
Germline considerations
Germline predisposition to haematological malignancy is increasingly recognised and is particularly relevant where a related stem cell donor is being considered.
Molecular monitoring
ctDNA and liquid biopsy considerations
Measurable residual disease assessment is the established analogue and is central to monitoring in several entities.
Single-cell & computation
Single-cell and algorithmic approaches
Haematological malignancy is the natural home of single-cell analysis, because the sample is already a cell suspension and no dissociation artefact is introduced. The question single-cell DNA sequencing answers here is one bulk sequencing simply cannot: whether two alterations reported at similar allele fraction sit in the same cell or in competing clones. That distinction changes prognosis and changes what a resistance mechanism would look like. Algorithm work spans high-sensitivity measurable residual disease detection, clonal phylogeny reconstruction across treatment timepoints, and integrated risk models combining cytogenetic, molecular and immunophenotypic features.
In practice
What a review of this disease typically surfaces
Across this group the recurring finding is a molecular profile that is out of date relative to the disease state. Haematological malignancies evolve clonally under treatment, and a profile from diagnosis may describe a disease that no longer exists. Germline predisposition is the other consistent gap, and it is most consequential before a related donor transplant.
Patterns observed across precision oncology case reviews. Every case differs; these are the questions worth checking, not conclusions about any individual patient.
Decisions
Treatment decision questions
Questions worth raising with a treating team when a decision is being made:
- Is the diagnostic work-up complete, including cytogenetics and molecular studies?
- Has risk stratification been performed?
- Has germline predisposition been considered, particularly before a related donor transplant?
Resistance
Resistance and recurrence questions
- Has the molecular profile been reassessed at relapse?
- Has clonal evolution been considered?
Trials
Clinical trial considerations
Molecular subgroup and measurable residual disease status frequently determine 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.