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Title: Lestaurtinib inhibition of the JAK/STAT signaling pathway in Hodgkin lymphoma inhibits proliferation and induces apoptosis
Author: Díaz Sánchez, Tania
Navarro Ponz, Alfons
Ferrer, Gerard
Gel, Bernat
Gaya, Anna
Artells i Prats, Rosa
Bellosillo, Beatriz
Garcia-Garcia, Mar
Serrano, Sergi
Martínez Pozo, Antonio
Monzó Planella, Mariano
Keywords: Malaltia de Hodgkin
Hodgkin's disease
Issue Date: 20-Apr-2011
Publisher: Public Library of Science (PLoS)
Abstract: Standard cytotoxic chemotherapy for Hodgkin Lymphoma (HL) has changed little in 30 years; the treatment for patients with relapsed or refractory disease remains challenging and novel agents are under development. JAK/STAT constitutive activation plays an important role in the pathogenesis of HL. Lestaurtinib is an orally bioavailable multikinase inhibitor that has recently been shown to inhibit JAK2 in myeloproliferative disorders. The potential role of Lestaurtinib in HL therapy is unknown. We have analyzed the effect of Lestaurtinib treatment in five HL cell lines from refractory patients, L-428, L-1236, L-540, HDML-2 and HD-MY-Z. At 48 h, a dose-dependent cell growth inhibition (23%-66% at 300 nM) and apoptotic increment (10%-64% at 300 nM) were observed. Moreover, Lestaurtinib inhibited JAK2, STAT5 and STAT3 phosphorylation and reduced the mRNA expression of its downstream antiapoptotic target Bcl-xL. In addition, we have analyzed the effect of Lestaurtinib treatment in lymph nodes from four classic HL patients. We observed a decrease in cell viability at 24 hours of treatment in three patients (mean decrease of 27% at 300 nM). Our findings provide, for the first time, a molecular rationale for testing JAK2 inhibitors, specifically Lestaurtinib, in HL patients.
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It is part of: PLoS One, 2011, vol. 6, num. 4
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ISSN: 1932-6203
Appears in Collections:Articles publicats en revistes (Fonaments Clínics)

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