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High-throughput Fluorometric Measurement of Potential Soil Extracellular Enzyme Activities
Published on: November 15, 2013
[Not Available]
Juliette Soret1, Jean-Jacques Kiladjian2
1Centre d'Investigations Cliniques, Hôpital Saint-Louis, APHP, Paris, France.
Abstract:
THE ROLE OF RUXOLITINIB IN THE TREATMENT OF MYELOPROLIFERATIVE NEOPLASMS: The discovery of the JAK2V617F mutation in 2005, present in 95% of polycythemia vera (PV) and in 55% of myelofibrosis (MF) patients, opened the way for a new era of targeted therapies for myeloproliferative neoplasms. Ruxolitinib was the first-in-class Janus Kinase (JAK) inhibitor approved for the management of these diseases. In PV patients, conventional treatment strategies including aspirin, phlebotomy, cytoreductive agents such as hydroxyurea and interferon, clearly provide clinical benefits. However, some patients develop resistance or intolerance to these treatments. Ruxolitinib has been approved for PV patients who are resistant to or intolerant of hydroxyurea, based on the results of the phase 3 RESPONSE study. This study showed that ruxolitinib improves hematocrit control, reduces splenomegaly, and ameliorate disease-related symptoms as compared with best available therapy. In MF patients, the only curative treatment is allogeneic stem cell transplantation, but it remains restricted to a limited group of patients with poor prognosis and who are eligible for such procedure associated with non-negligible transplant-related mortality. Other treatments are palliative and unlikely to prolong survival. Ruxolitinib has been approved in the United States for MF patients with intermediate or high-risk disease, and in Europe for disease-related splenomegaly or symptoms in adults with MF, based on phase 3 COMFORT-I and COMFORT-II studies. These studies showed that ruxolitinib was able to reduce splenomegaly, ameliorate symptoms, and improve survival. However, the journey is not finished yet since there are still important unmet needs for MF patients, including improvement in cytopenias, and significant modification of disease natural history.
Insights
Ruxolitinib, a Janus Kinase (JAK) inhibitor, offers targeted therapy for myeloproliferative neoplasms like polycythemia vera and myelofibrosis. It effectively manages symptoms and improves outcomes in patients resistant to conventional treatments.
Area of Science:
- Hematology
- Oncology
- Pharmacology
Background:
- The JAK2V617F mutation is a key driver in myeloproliferative neoplasms (MPNs), including polycythemia vera (PV) and myelofibrosis (MF).
- Targeted therapies offer new treatment avenues for MPNs, addressing limitations of conventional management.
Purpose of the Study:
- To review the role and efficacy of ruxolitinib, a Janus Kinase (JAK) inhibitor, in treating PV and MF.
- To highlight ruxolitinib's impact on patient outcomes and symptom management in MPNs.
Main Methods:
- Review of Phase 3 clinical trials (RESPONSE, COMFORT-I, COMFORT-II) evaluating ruxolitinib in PV and MF.
- Analysis of ruxolitinib's efficacy in improving hematocrit control, reducing splenomegaly, alleviating symptoms, and enhancing survival.
Main Results:
- Ruxolitinib demonstrated significant improvements in hematocrit control and symptom burden in PV patients resistant to hydroxyurea.
- In MF patients, ruxolitinib effectively reduced spleen size, improved symptoms, and was associated with improved survival in intermediate/high-risk disease.
Conclusions:
- Ruxolitinib is a valuable targeted therapy for specific patient populations with PV and MF, offering benefits beyond best available therapy.
- Despite advancements, unmet needs remain in MPN treatment, including managing cytopenias and altering disease progression.

