Ten years that changed MPNs: from controlling symptoms to altering the disease
Between 2015 and 2026, research in polycythemia vera (PV), essential thrombocythemia (ET) and myelofibrosis (MF) has changed significantly. A decade ago, the conversation focused mainly on controlling blood counts, preventing complications and relieving symptoms. Today, it also includes genetic profiles, mutation burden, targeted therapies, quality of life and the active participation of patients in research. The path is far from complete. Many questions remain open. But for people living with a myeloproliferative neoplasm (MPN), the map of the disease has changed.
Where we were ten years ago
Until 2008, these conditions were known as chronic myeloproliferative disorders, a term that described bone marrow producing too many blood cells but did not fully explain the biological origin of the problem.
The shift to the term myeloproliferative neoplasms reflected a more accurate understanding of their biology. After the discovery of the JAK2 V617F mutation in 2005, it became clear that these diseases arise from a clonal expansion, meaning a blood stem cell acquires an alteration and passes that signal to its descendants.
This change was not only about language. It also changed the research question. Controlling blood counts was no longer enough. Researchers began to ask whether treatments could act on the diseased clone itself and potentially modify the course of the disease.
A decade ago, treatment for MPNs relied on familiar tools: aspirin, phlebotomy in polycythemia vera and hydroxyurea to reduce blood counts. Ruxolitinib, a JAK inhibitor, had opened a new stage in myelofibrosis and in polycythemia vera resistant or intolerant to hydroxyurea, especially because of its impact on spleen size and symptoms.
Still, important needs remained: options for patients with very low platelets, better approaches for anemia, strategies with an effect on the diseased clone and more precise ways to diagnose and classify each condition.
A decade of milestones
In 2015, ruxolitinib was approved in Europe for polycythemia vera, and the revised IPSET-thrombosis score helped refine risk classification in essential thrombocythemia.
In 2016, the WHO classification formally recognized prefibrotic myelofibrosis and lowered the diagnostic thresholds for polycythemia vera. This helped identify cases that could previously have been missed or classified less precisely.
Between 2017 and 2018, prognostic models with a stronger genetic component emerged, including MIPSS70, MIPSS70+ v2.0, GIPSS and MYSEC-PM. Prognosis began to depend not only on age, symptoms or blood counts, but also on mutation profiles and cytogenetics.
In 2019, the EMA approved ropeginterferon alfa-2b for polycythemia vera, and the FDA approved fedratinib for myelofibrosis. These developments showed that the field was beginning to diversify.
In 2021, the LOW-PV study showed that adding ropeginterferon to phlebotomy could improve hematocrit control even in low-risk patients. That same year, the FDA approved BESREMi for polycythemia vera.
In 2022, a study published in Nature reconstructed the life history of MPNs and showed that the JAK2 mutation can be acquired many years before diagnosis, sometimes very early in life. This idea had both scientific and emotional significance: for many people, it helps clarify that the initial mutation was not caused by something they did as adults.
Between 2022 and 2023, new JAK inhibitors helped address some unmet needs. Pacritinib was approved in the United States for patients with myelofibrosis and low platelets, and momelotinib opened an important pathway for patients with myelofibrosis and anemia.
In 2024 and 2025, the field continued to advance through real-world data, national registries, new combinations, more sophisticated prognostic models and targeted treatments against specific alterations, including antibodies against mutant CALR, still under clinical investigation.
In 2026, two recent U.S. approvals marked another relevant moment for the MPN community: MIMRYLO™ (rusfertide) for adults with polycythemia vera and BESREMi® (ropeginterferon alfa-2b) for adults with essential thrombocythemia.
Understanding the disease more deeply
One of the great drivers of the past decade has been a deeper biological understanding of MPNs. The discovery of CALR mutations in late 2013 helped explain many cases that previously had no identified driver mutation. Today, that same protein has become one of the most promising targets in MPN research.
Next-generation sequencing has also changed clinical practice. Mutations such as ASXL1, SRSF2, EZH2, IDH1, IDH2 or TP53 can provide relevant prognostic information and help guide clinical decisions, especially in myelofibrosis.
«The mutation was not caused by anything you did as an adult; in most cases, it was already present in childhood. What we still do not fully understand is what determines whether it takes eleven years to manifest or fifty-four.» Central idea of the Nature (2022) study on the origin of MPNs.
Another increasingly common concept is variant allele frequency, or VAF. This number indicates what proportion of the analyzed genetic material comes from cells carrying a specific mutation.
In simple terms, VAF helps measure not only how much the disease is reflected in blood counts, but how present the mutated clone is in the analyzed sample. Its value is especially important in research, because it can show whether a treatment is reducing the diseased clone itself and not only controlling its consequences. However, it should be interpreted with care: VAF is not yet a routine treatment goal for every patient, and small changes between tests should not be interpreted without medical context.
From relieving symptoms to trying to modify disease
For years, the main benchmark for many treatments was reducing spleen size, improving symptoms or controlling blood counts. Today, research is aiming higher: modifying the course of the disease.
Two areas stand out.
The first is interferon, particularly ropeginterferon alfa-2b. Long-term follow-up data in polycythemia vera have shown not only hematologic control, but also sustained reduction in mutation burden in some patients. This does not mean that every patient should receive interferon, or that the benefit is the same for everyone, but it has strengthened the role of interferon in the discussion around disease-modifying potential.
The second area includes therapies targeting mutant CALR. Early data for antibodies such as INCA033989 have generated significant interest because they point toward a highly specific strategy: recognizing cells with mutant calreticulin and acting on them. These data are promising, but they remain within clinical research. These therapies are not approved and must be evaluated in larger studies.
There have also been results that remind us why caution matters. Some drugs have shown activity on spleen size but did not sufficiently meet goals related to symptoms or quality of life. This evolution is important: the field is learning that improving a clinical variable is not enough if the person does not feel better.
Spain: from participation to evidence generation
Spain has played an increasingly visible role in MPN research over the past decade.
The work of GEMFIN, the Spanish cooperative group dedicated to myeloproliferative neoplasms, has contributed to consensus documents, registries and real-world studies. These data matter because they reflect how diseases evolve outside the controlled setting of a clinical trial.
The Spanish Myelofibrosis Registry, the polycythemia vera and essential thrombocythemia registries, studies on resistance to hydroxyurea, artificial intelligence-based prognostic models and real-world series with new treatments have placed Spanish teams within the international conversation.
There are still challenges. A medicine being approved in Europe does not always mean it is available or reimbursed in every country. Access remains a key part of the conversation.
The patient voice: from testimony to part of the method
One of the most important changes of the past decade has been the role of patients. For a long time, clinical trials focused mainly on clinical variables: blood counts, spleen size, progression or thrombosis. Today, symptoms, fatigue, daily life impact, treatment burden and quality of life are much more visible.
The international MPN LANDMARK survey showed an important gap between what many patients prioritized and what many physicians prioritized. For patients, symptoms and quality of life were central concerns. For physicians, prevention of complications and disease progression often carried more weight.
Both perspectives are necessary. Progress means bringing them together.
Tools such as the MPN-10 questionnaire have helped better incorporate patient experience into clinical trials. Patient associations and foundations are increasingly involved in congresses, reviews, educational projects and research programs.
The patient's voice is part of the method
At Global MPN Scientific Foundation, this change is part of our mission: to connect patients, families, healthcare professionals, researchers and organizations so that the experience of living with an MPN helps shape the future of these diseases. The patient voice should no longer be an addition at the end of the conversation. It should be part of the method.
What comes next
The next decade has already begun. Some research lines aim to reduce phlebotomy burden in polycythemia vera. Others are exploring strategies directed at mutant CALR, new immunological approaches, treatment combinations, better prognostic tools and smarter use of real-world data.
Hematopoietic stem cell transplantation will remain a relevant option for selected patients with myelofibrosis, but its indication will continue to require a highly individualized assessment.
Registries and prognostic models will also be key to moving toward more precise medicine, able to better adapt decisions to each person rather than relying only on broad risk categories.
Ten years later, MPNs remain complex chronic diseases. Not everything has been solved. But they are diagnosed more accurately, understood more deeply and researched from angles that were barely part of the conversation before.
For people living with an MPN, this is not an abstract promise. It is a horizon that has moved.
This content is intended for informational and educational purposes only. It does not replace medical advice and does not constitute a treatment recommendation. Treatment availability may vary by country. Treatment decisions should always be discussed with a hematologist or MPN specialist.
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