Scientists followed people with chronic blood cancers for many years. They found big DNA differences between patients whose disease stayed calm and those whose disease got worse.
These DNA clues could help doctors spot problems early, check how well treatments work, and see signs of danger years before a patient feels sick.
What Are Chronic Blood Cancers?
Myeloproliferative neoplasms, or MPNs, are rare cancers that start in the bone marrow – the place where blood cells are made. In MPNs, the marrow makes some blood cells too fast.
About 40,000 people in the UK live with an MPN and roughly 4,000 new cases appear each year. The cancers grow slowly. They often begin with tiny DNA changes early in life, then collect more changes over decades.
Most MPNs have mutations in the JAK2, CALR or MPL genes. Around 10 % of patients do not show any of these mutations.
When the common mutations are missing, doctors may rely on how bone‑marrow cells look under a microscope. This can lead to treating someone with chemotherapy even if the DNA does not prove a real cancer.
Why Some Cancers Get Worse
People with chronic blood cancers can have very different experiences. Some feel fine for many years and need only light treatment. Others eventually develop serious problems like leukemia or myelofibrosis (scar tissue in the marrow).
Doctors cannot always tell in advance who will stay stable and who will get worse. The researchers asked whether DNA changes could give a clue.
They studied 30 patients, mostly with MPNs. They used whole‑genome sequencing and collected almost 8,000 blood test results, treatment notes, and disease records. Over 450 blood samples were examined, some taken over a 25‑year period.
Making Family Trees of Blood Cells
By looking at DNA from blood cells, the team built genetic “family trees.” These trees show how groups of identical cells – called clones – appear and grow.
Patients whose disease stayed stable had blood cells that changed very little. Those whose disease progressed kept picking up new DNA mutations.
This means the future worsening of a cancer may be written in the DNA years before doctors can see any symptoms.
When No Common Mutations Are Found
The scientists also looked at patients without JAK2, CALR or MPL mutations. They built trees from about 200 blood‑cell genomes and saw changes that looked normal for aging, not for cancer.
These results suggest some people labeled as having an MPN may actually just have age‑related changes. New British Society for Haematology guidelines now recommend calling such cases “thrombocytosis without JAK2/CALR/MPL mutations” instead of labeling them as cancer right away.
Genomics Could Become a Routine Check‑Up
Using DNA tests regularly could help doctors separate calm disease from cancers that will get worse, clear up uncertain diagnoses, and guide more precise treatments.
In the future, regular DNA checks might flag high‑risk patients years before their condition declines, allowing early action while avoiding unnecessary treatment for those whose blood changes are harmless.
One Patient’s Long Journey
Alan Everitt, 77, has been treated at Cambridge University Hospitals for more than 30 years. He was first diagnosed in 1992 with essential thrombocythemia, a type of MPN that makes too many platelets.
Later his disease turned into myelofibrosis, which scars the bone marrow, and he also got several skin cancers. Alan says the long‑term care he received gave him confidence and hopes his participation in research will help future patients.
This work was supported by Wellcome and Cancer Research UK.