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|Ref Type||Journal Article|
|Authors||Verger E, Soret-Dulphy J, Maslah N, Roy L, Rey J, Ghrieb Z, Kralovics R, Gisslinger H, Grohmann-Izay B, Klade C, Chomienne C, Giraudier S, Cassinat B, Kiladjian JJ|
|Title||Ropeginterferon alpha-2b targets JAK2V617F-positive polycythemia vera cells in vitro and in vivo.|
|Abstract Text||Polycythemia vera is characterized by the acquisition of the JAK2V617F mutation. Recommended treatments include hydroxyurea and interferon-alpha. Several groups have reported a reduction in the JAK2 mutant allele burden in interferon-treated patients, but significance of this observation is questioned. We characterized the activity of ropeginterferon alpha-2b, a novel form of interferon-alpha recently shown to be safe and efficacious in polycythemia vera. Ropeginterferon was able to inhibit the proliferation of the HEL, UKE-1, and UT-7 JAK2-mutant cell lines while sparing JAK2-wild-type UT-7 and normal CD34+ cells growth. In vitro treatment of erythroid progenitors derived from PV patients showed that ropeginterferon could considerably inhibit the growth of endogenous erythroid colonies, a hallmark of polycythemia vera. Finally, we could study in sequential samples the clonal architecture of erythroid progenitors derived from patients included in a randomized study comparing hydroxyurea to ropeginterferon. After 1 year of treatment with ropeginterferon, the ratio of JAK2-mutated to wild-type colonies grown from bone marrow progenitors was reduced by 64%, compared to 25% in patients receiving hydroxyurea. This study shows that ropeginterferon has a potent targeted activity against JAK2-mutant cells and is able to drastically reduce the proportion of malignant progenitors in patients treated with this drug.|
|Molecular Profile||Treatment Approach|
|Gene Name||Source||Synonyms||Protein Domains||Gene Description||Gene Role|
|Drug Name||Trade Name||Synonyms||Drug Classes||Drug Description|
|Ropeginterferon||RopegInterferon alpha-2b|Ropeg|Besremi||Ropeginterferon is polyethylene glycol (PEG)-conjugated recombinant interferon alpha, subtype 2b, which may result in reduced tumor cell proliferation and colony growth (PMID: 30287855).|
|Gene||Variant||Impact||Protein Effect||Variant Description||Associated with drug Resistance|
|Molecular Profile||Indication/Tumor Type||Response Type||Therapy Name||Approval Status||Evidence Type||Efficacy Evidence||References|
|JAK2 V617F||acute megakaryocytic leukemia||sensitive||Ropeginterferon||Preclinical - Cell culture||Actionable||In a preclinical study, a megakaryoblastic leukemia cell line expressing JAK2 V617F demonstrated inhibition of cell proliferation in culture when treated with Ropeginterferon (PMID: 30287855).||30287855|
|JAK2 V617F||myeloproliferative neoplasm||sensitive||Ropeginterferon||Preclinical - Cell culture||Actionable||In a preclinical study, Ropeginterferon treatment resulted in dose-dependent inhibition of cell proliferation in myeloproliferative neoplasm cell lines harboring JAK2 V617F in culture (PMID: 30287855).||30287855|
|JAK2 V617F||polycythemia vera||sensitive||Ropeginterferon||Clinical Study - Cohort||Actionable||In a clinical study using data from a Phase III trial, polycythemia vera patients demonstrated significant reduction in the median JAK2 V617F mutational burden at 12 months following treatment with Ropeginterferon compared to Droxia (hydroxyurea) (13.8% vs. 33.2%; p<0.02) (PMID: 30287855; NCT01949805).||30287855|
|JAK2 V617F||polycythemia vera||sensitive||Ropeginterferon||Preclinical - Patient cell culture||Actionable||In a preclinical study, patient-derived erythroid progenitors harboring JAK2 V617F demonstrated sensitivity to Ropeginterferon in culture (PMID: 30287855).||30287855|