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A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors
Published on: December 7, 2014
Differential expression of JAK2 and Src kinase genes in response to hydroxyurea treatment in polycythemia vera and
Enriqueta Albizua1, Miguel Gallardo, Santiago Barrio
1Servicio de Hematología, Hospital Universitario 12 de Octubre, Avenida Córdoba s/n, 28041, Madrid, Spain.
Abstract:
This study investigates the differential gene expression profile of JAK2(V617F)-positive myeloproliferative neoplasm (MPN) patients, with and without response to hydroxyurea (HU) treatment. Twenty-one polycythemia vera, 28 essential thrombocythemia, eight secondary erythrocytosis, and 30 controls were studied. Thirty-four genes were overexpressed in patients who did not respond to HU. Of these, some participate in proliferative pathways: MAPK, AKT, Src kinase (SFK), and JAK2 pathway. JAK2 allele burden was similar between groups of responders and nonresponder. A molecular fingerprint distinguishes JAK2(V617F)-positive MPN patients without response to HU treatment, with overexpression of JAK2, MAPK14, PIK3CA, and SFK genes.
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