Reference Detail

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.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Blood cancer journal	8	10	2018 10 04	94	Blood Cancer J

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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.

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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
Ropeginterferon	Ropeginterferon	4	1

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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).

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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
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
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	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

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