Myeloproliferative Neoplasms
Myeloproliferative neoplasms are clonal disorders producing an excess of mature blood cells. They are defined molecularly, and the specific driver alteration carries prognostic weight.
Disease categories
Major disease categories
- Polycythaemia vera
- Essential thrombocythaemia
- Primary myelofibrosis
- Chronic myeloid leukaemia
- Chronic neutrophilic leukaemia
Molecular
Molecular considerations
JAK2 V617F, CALR and MPL alterations are the principal drivers in the BCR::ABL1-negative neoplasms. Chronic myeloid leukaemia is defined by BCR::ABL1. Additional high-molecular-risk alterations including ASXL1, EZH2, SRSF2 and IDH1/2 inform prognosis in myelofibrosis.
Markers commonly discussed in myeloproliferative neoplasms
- JAK2 V617F
- CALR
- MPL
- BCR::ABL1
- ASXL1
- EZH2
- Bone marrow fibrosis grade
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
Driver testing is integral to diagnosis. Extended panels are used for risk assessment in myelofibrosis.
Germline
Germline considerations
Familial predisposition to myeloproliferative neoplasms is described and considered where family history is suggestive.
Molecular monitoring
ctDNA and liquid biopsy considerations
Quantitative monitoring of the driver allele burden is used in research and practice discussion.
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 driver mutation testing been completed, including CALR and MPL where JAK2 is negative?
- Has BCR::ABL1 been excluded?
- Is thrombotic risk documented and being managed?
Resistance
Resistance and recurrence questions
- Has progression to myelofibrosis or acute leukaemia been considered where the clinical picture changes?
Trials
Clinical trial considerations
Driver alteration and risk score 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.