000147818 001__ 147818
000147818 005__ 20250107161405.0
000147818 0247_ $$2doi$$a10.1371/journal.pone.0018856
000147818 0248_ $$2sideral$$a129732
000147818 037__ $$aART-2011-129732
000147818 041__ $$aeng
000147818 100__ $$aDiaz, Tania
000147818 245__ $$aLestaurtinib Inhibition of the JAKSTAT Signaling Pathway in Hodgkin Lymphoma Inhibits Proliferation and Induces Apoptosis
000147818 260__ $$c2011
000147818 5060_ $$aAccess copy available to the general public$$fUnrestricted
000147818 5203_ $$aStandard 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.
000147818 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000147818 590__ $$a4.092$$b2011
000147818 591__ $$aBIOLOGY$$b12 / 85 = 0.141$$c2011$$dQ1$$eT1
000147818 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000147818 700__ $$aNavarro, Alfons
000147818 700__ $$aFerrer, Gerardo
000147818 700__ $$aGel, Bernat
000147818 700__ $$aGaya, Anna
000147818 700__ $$aArtells, Rosa
000147818 700__ $$aBellosillo, Beatriz
000147818 700__ $$0(orcid)0000-0003-2078-8205$$aGarcia-Garcia, Mar
000147818 700__ $$aSerrano, Sergi
000147818 700__ $$aMartínez, Antonio
000147818 700__ $$aMonzo, Mariano
000147818 700__ $$aNogales-Gadea, Gisela
000147818 773__ $$g6, 4 (2011), e18856 [7 pp.]$$pPLoS One$$tPLoS ONE$$x1932-6203
000147818 8564_ $$s837269$$uhttps://zaguan.unizar.es/record/147818/files/texto_completo.pdf$$yVersión publicada
000147818 8564_ $$s3210153$$uhttps://zaguan.unizar.es/record/147818/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000147818 909CO $$ooai:zaguan.unizar.es:147818$$particulos$$pdriver
000147818 951__ $$a2025-01-07-14:05:38
000147818 980__ $$aARTICLE