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Ref Type | Journal Article | ||||||||||||
PMID | (30287855) | ||||||||||||
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. | ||||||||||||
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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 |
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Gene Name | Source | Synonyms | Protein Domains | Gene Description | Gene Role |
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Therapy Name | Drugs | Efficacy Evidence | Clinical Trials |
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Ropeginterferon | Ropeginterferon | 4 | 1 |
Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
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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 |
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Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
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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 |
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 | 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 |