Anaplastic lymphoma kinase ALK inhibitor response in neuroblastoma is highly correlated with ALK mutation status, ALK mRNA and protein levelsReportar como inadecuado




Anaplastic lymphoma kinase ALK inhibitor response in neuroblastoma is highly correlated with ALK mutation status, ALK mRNA and protein levels - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Cellular Oncology

, Volume 34, Issue 5, pp 409–417

First Online: 31 May 2011Accepted: 01 May 2011DOI: 10.1007-s13402-011-0048-2

Cite this article as: Duijkers, F.A.M., Gaal, J., Meijerink, J.P.P. et al. Cell Oncol. 2011 34: 409. doi:10.1007-s13402-011-0048-2

Abstract

BackgroundIn pediatric neuroblastoma NBL, high anaplastic lymphoma kinase ALK levels appear to be correlated with an unfavorable prognosis, regardless of ALK mutation status. This suggests a therapeutic role for ALK inhibitors in NBL patients. We examined the correlation between levels of ALK, phosphorylated ALK pALK and downstream signaling proteins and response to ALK inhibition in a large panel of both ALK mutated and wild type WT NBL cell lines.

MethodsWe measured protein levels by western blot and ALK inhibitor sensitivity TAE684 by viability assays in 19 NBL cell lines of which 6 had a point mutation and 4 an amplification of the ALK gene.

ResultsALK 220 kDa p = 0.01 and ALK 140 kDa p = 0.03 protein levels were higher in ALK mutant than WT cell lines. Response to ALK inhibition was significantly correlated with ALK protein levels p < 0.01. ALK mutant cell lines n = 4 were 14,9 fold p < 0,01 more sensitive to ALK inhibition than eight WT cell lines.

ConclusionNBL cell lines often express ALK at high levels and are responsive to ALK inhibitors. Mutated cell lines express ALK at higher levels, which may define their superior response to ALK inhibition.

KeywordsALK Kinase inhibitor Neuroblastoma PHOX2B TAE684 Electronic supplementary materialThe online version of this article doi:10.1007-s13402-011-0048-2 contains supplementary material, which is available to authorized users.

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Autor: Floor A. M. Duijkers - José Gaal - Jules P. P. Meijerink - Pieter Admiraal - Rob Pieters - Ronald R. de Krijger - Max

Fuente: https://link.springer.com/



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