Acute Myeloid Leukaemia
Acute myeloid leukaemia is classified and risk-stratified molecularly. Cytogenetic and molecular findings are not supplementary information here — they define the disease entity and determine the treatment discussion.
Disease categories
Major disease categories
- AML with recurrent genetic abnormalities
- AML with myelodysplasia-related changes
- Therapy-related myeloid neoplasm
- Acute promyelocytic leukaemia
- AML not otherwise specified
Molecular
Molecular considerations
FLT3-ITD and FLT3-TKD, NPM1, CEBPA, IDH1 and IDH2, TP53 and RUNX1 status all inform classification and risk. Acute promyelocytic leukaemia, defined by PML::RARA, is a distinct entity requiring urgent recognition.
Markers commonly discussed in acute myeloid leukaemia
- FLT3-ITD / TKD
- NPM1
- CEBPA
- IDH1 / IDH2
- TP53
- RUNX1
- PML::RARA
- 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 and a molecular panel are integral to diagnosis, and turnaround time matters because results influence initial decisions.
Germline
Germline considerations
Germline predisposition — including RUNX1, CEBPA, DDX41 and GATA2 — is increasingly recognised, and is particularly important 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 monitoring approach.
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:
- Is the full cytogenetic and molecular profile available, and how quickly?
- Has risk stratification been performed using it?
- Has germline predisposition been considered before a family donor is selected?
Resistance
Resistance and recurrence questions
- Has the molecular profile been repeated at relapse, since it frequently changes?
- Has clonal evolution been considered?
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.