Leukaemia
Leukaemia classification is molecular in a way few solid tumours are. Cytogenetics and molecular findings define disease entities, determine risk group and inform monitoring — they are not supplementary information.
Disease categories
Major disease categories
- Acute myeloid leukaemia
- Acute lymphoblastic leukaemia
- Chronic myeloid leukaemia
- Chronic lymphocytic leukaemia
- Myelodysplastic syndromes
- Myeloproliferative neoplasms
Molecular
Molecular considerations
In acute myeloid leukaemia, FLT3, NPM1, IDH1, IDH2, CEBPA and TP53 status inform classification and risk. Chronic myeloid leukaemia is defined by BCR::ABL1, with quantitative monitoring central to management. In chronic lymphocytic leukaemia, IGHV mutational status, TP53 alteration and del(17p) carry recognised weight. Philadelphia-positive and Philadelphia-like acute lymphoblastic leukaemia are distinguished molecularly.
Markers commonly discussed in leukaemia
- BCR::ABL1
- FLT3-ITD / TKD
- NPM1
- IDH1 / IDH2
- TP53
- del(17p)
- IGHV status
- Karyotype
- 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 and molecular panels are integral to diagnosis and classification rather than optional additions.
Germline
Germline considerations
Germline predisposition to haematological malignancy is increasingly recognised — including RUNX1, CEBPA, DDX41 and GATA2 — and is particularly relevant where a related stem cell donor is being considered.
Molecular monitoring
ctDNA and liquid biopsy considerations
Measurable residual disease assessment, by flow cytometry or molecular methods, is the established analogue in haematology and is central to monitoring.
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.
In practice
What a review of this disease typically surfaces
Cases arrive most often with an incomplete molecular panel, or with results that predate the current disease state. In acute myeloid leukaemia the profile at relapse frequently differs from diagnosis, and treating the original profile as current is a recognised error. Germline predisposition is the other recurring gap, and it matters most when a sibling is being considered as a stem cell donor — a question that is much harder to revisit after 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 full cytogenetic and molecular profile available and current?
- Has risk stratification been performed using it?
- Has germline predisposition been considered, especially where a family donor is planned?
Resistance
Resistance and recurrence questions
- Has a resistance alteration been sought — for example a kinase domain alteration in chronic myeloid leukaemia?
- Has the molecular profile been reassessed at relapse, as it frequently changes?
Trials
Clinical trial considerations
Molecular subgroup and measurable residual disease status are frequently determinative for 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.