Myelodysplastic Syndromes
Myelodysplastic syndromes are clonal marrow disorders producing ineffective blood production, with a risk of progression to acute myeloid leukaemia. Risk stratification drives essentially the whole management discussion.
Disease categories
Major disease categories
- MDS with low blasts
- MDS with increased blasts
- MDS with isolated del(5q)
- MDS with SF3B1 mutation
- Therapy-related MDS
Molecular
Molecular considerations
SF3B1, TP53, ASXL1, SRSF2, RUNX1 and TET2 alterations inform classification and prognosis. TP53 status, particularly biallelic alteration, identifies a distinct high-risk group. del(5q) defines a specific entity.
Markers commonly discussed in myelodysplastic syndromes
- SF3B1
- TP53 (mono- vs biallelic)
- ASXL1
- SRSF2
- RUNX1
- del(5q)
- Karyotype
- Blast percentage
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 classification and to risk scoring.
Germline
Germline considerations
Germline predisposition is an important consideration in younger patients and before a related donor transplant.
Molecular monitoring
ctDNA and liquid biopsy considerations
Marrow assessment remains the established route; circulating assessment is investigational.
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 a formal risk score been calculated using cytogenetics and molecular findings?
- Has TP53 status been assessed, including whether alteration is biallelic?
- Has germline predisposition been considered before a family donor is selected?
Resistance
Resistance and recurrence questions
- Has the marrow been reassessed if blood counts change?
- Has progression to acute leukaemia been excluded?
Trials
Clinical trial considerations
Risk group and specific molecular alterations 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.