Long-term genetic tracking of patients with chronic blood cancers is revealing hidden patterns in how these diseases develop and progress.
Following patients over time has revealed key genetic differences between blood cancers that remain stable and those that become more aggressive. The findings also show how DNA data could sharpen diagnoses, improve how patients are monitored, and give doctors a clearer view of how treatments are working. Together, this points to a future where routine genetic testing plays a larger role in standard NHS care.
In a study published in Cancer Discovery, scientists from the Wellcome Sanger Institute and their collaborators examined both genetic data and clinical records from patients with chronic blood cancers. By tracing the lineage of blood cells, they explored how these diseases develop over decades. The results are also being presented at the American Association of Cancer Research (AACR) Conference in San Diego.
Myeloproliferative neoplasms (MPNs) are one form of chronic blood cancer. These rare disorders begin in the bone marrow, where blood cells are produced in excessive and uncontrolled numbers. About 40,000 people in the UK are living with MPNs, and roughly 4,000 new cases are diagnosed each year. These conditions tend to progress slowly and are driven by mutations, or changes in DNA, that can arise early in life and build up over time.
Most MPN cases are linked to mutations in the JAK2, CALR, or MPL genes. However, around 10 percent of patients do not carry any of these genetic changes. In these cases, diagnosis often relies on how bone marrow cells appear under a microscope. As a result, some patients may receive treatments such as chemotherapy without clear genetic evidence of cancer.
Challenges in Predicting Disease Progression
The course of these cancers varies widely. Some patients remain stable for years and need only minimal treatment, while others develop more serious conditions such as leukemia or scarring in the bone marrow. Doctors still struggle to predict which path a patient’s disease will take.
To address this, the research team investigated whether genetic analysis could help forecast disease progression and clarify whether patients without common mutations truly have cancer.
They followed 30 patients with chronic blood cancers, mostly MPNs, combining whole genome sequencing with detailed medical records. The dataset included nearly 8,000 blood test results, along with treatment histories and disease outcomes. In total, more than 450 samples were analyzed, with some patients monitored for up to 25 years during routine care.
By linking long-term clinical follow-up at Cambridge University Hospitals NHS Foundation Trust with genomic analysis at the Sanger Institute, the team tracked how blood cell populations changed over time. Using DNA to build cellular “family trees,” they identified the origins of cancer clones, groups of genetically identical cells that eventually drove disease progression.
Distinct Evolutionary Patterns
The study revealed clear differences in how these cancers evolve. Patients whose disease stayed stable had blood cells that remained genetically consistent, without accumulating new mutations. In contrast, patients whose condition worsened showed a steady buildup of DNA changes over time.
These results suggest that the course of disease is often set years in advance, with early genetic signals appearing long before symptoms become noticeable.
The researchers also examined patients who lacked the usual genetic markers of MPNs. By studying “family trees” built from about 200 blood cell genomes, they found patterns that matched normal aging rather than cancer-related activity.
This finding challenges the assumption that all patients with certain bone marrow features have a true blood cancer. It suggests that some individuals may be misclassified and could benefit from different management strategies. The results support new British Society for Haematology guidelines for evaluating patients without JAK2, CALR, or MPL mutations, aimed at improving diagnosis and care.
Clinical Implications and Future Directions
The study highlights the growing importance of genomic data in cancer care and its potential to guide more precise treatments. Researchers say regular genetic testing could one day help identify patients at high risk of progression years earlier, allowing doctors to step in sooner.
Dr Daniel Leongamornlert, first author at the Wellcome Sanger Institute, said: “We followed patients with myeloproliferative neoplasms over many years and used genome sequencing and clinical history to trace how blood cell populations changed over time. By reconstructing the ancestry of cells, we were able to see different evolutionary patterns between patients who had stable disease compared to others who progressed.”
Dr Dani Skirrow, Research Information Manager at Cancer Research UK, who part-funded the study, said: “We’re in a golden age of research where advances in technology mean we can rapidly read DNA to find the errors in the code that can lead to cancer. Collaboratively, our researchers have read huge amounts of DNA to build up a detailed picture of how certain blood cancers can start, grow, and behave, revealing some changes that could help us predict cancer years in advance. This type of discovery research is essential to improve how we monitor people at risk of blood cancer, and to help us find better ways to prevent, detect, and treat the disease so people can live longer, better lives.”
Patient Perspective
Dr Jyoti Nangalia, senior author at the Wellcome Sanger Institute and Honorary Consultant Hematologist at Cambridge University Hospitals NHS Foundation Trust, said: “These are patients we have cared for and followed in our clinic for over 15 years. It can be incredibly difficult to predict how their cancers might change over time. By combining long-term clinical care with regular genomic analysis, we’ve been able to watch how the genetic code of their disease evolves in advance of clinical changes. The patterns we have found will help doctors develop better monitoring strategies, refine diagnosis and lead to better patient outcomes in the long run.”
Alan Everitt, 77, a patient at Cambridge University Hospitals NHS Foundation Trust, was diagnosed with essential thrombocythaemia (ET), a type of MPN, in 1992. ET causes the body to produce too many platelets, which are involved in blood clotting. Over time, his condition progressed to myelofibrosis, a disease marked by scarring in the bone marrow, along with recurring skin cancers.
Alan Everitt, from Hardwick, Cambridgeshire, said: “It’s been reassuring to be cared for over so many years by both the hematology and plastic surgery teams at Addenbrooke’s Hospital in Cambridge. I have always felt well supported and I’m grateful for the care and feedback at every step. Living with a blood cancer for such a long time has come with many challenges, and I hope that taking part in this research will help make a difference for future patients whose cancer is likely to progress over time, as mine has.”
Reference: “Genomic evolution and natural history of myeloproliferative neoplasms on therapy” by Daniel Leongamornlert, Joe Lee, Aleksandra E. Kamizela, Ken To, Daniel Myers, Nicholas Williams, Kudzai Nyamondo, Xin Wang, Jing Guo, Ruchira K. Dissanayake, Jane Price, Amer J. Durrani, Jonathan Lambert, Michael Spencer Chapman, John E. Pimanda, E Joanna Baxter, Anthony R. Green, Anna L. Godfrey and Jyoti Nangalia, 20 April 2026, Cancer Discovery.
DOI: 10.1158/2159-8290.CD-26-0410
This research was supported in part by Wellcome and Cancer Research UK. A full list of acknowledgements can be found in the publication.
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