Background. Most chronic myeloid leukemia patients who receive imatinib as first line-terapy will obtain, after 12 months treatment, complete cytogenetic and molecular response . However several cases will not achieve molecular response, but their innate mechanism(s) of resistance remain poorly understood. We tried to explore the molecular events involved in innate resistance in CML. Study design. Five patients who were molecular “non responder” and seven “major” responder were investigated by using the expression profile of a set of 380 genes. Multiple testing procedure (MTP), Significance Analysis of Microarrays (SAM), Empirical Bayes Analysis of Microarrays (EBAM), False Discovery Rate (FDR) and support vector machine with linear kernel (SVM-RFE) were used for comparative analysis. Results. 323/380 genes (85%) were overexpressed in the non responder group compared with the responder ones. Following a very stringent statistical analysis, comprensive of all analysis used, a list of 26 genes was identified, in which overexpression in non-responders was highly statistically significant. These genes are involved in signal trasduction and transcription factors, apoptosis, cell adhesion and cycle progression. Discriminative power of proposed gene set was estimated by two different statistical methods which yielded a correct prediction of the drug response for each patient used as test sample. Conclusion. Our study identified a set of twenty-six genes involved in resistance to imatinib, which may be used as clinical predictors or therapeutic targets. We consider some of them of particular interest: IGFBP2, CDC37; MAPK3, ETS1, PEA15. Epigenetic mechanisms, such as genome-wide promoter hypomethilation, may be involved as the basic mechanism for innate resistance in CML.
|Data di pubblicazione:||2007|
|Titolo:||Gene Expression Profile of Chronic Myeloid Leukemia Innately Resistant to Imatinib|
|Autori:||CAMMARATA, G; AUGUGLIARO, L; LA ROSA, M; TURRI, D; RIZZO, V; MARFIA, A; AGUELI, C; DAGNINO, L; GIUSTOLISI, R; MIRTO, S; MINEO, A; SANTORO, A|
|Tipologia:||Articolo su rivista|
|Citazione:||CAMMARATA, G., AUGUGLIARO, L., LA ROSA, M., TURRI, D., RIZZO, V., MARFIA, A., et al. (2007). Gene Expression Profile of Chronic Myeloid Leukemia Innately Resistant to Imatinib. CLINICAL LEUKEMIA, 1(4), 234-242.|
|Appare nelle tipologie:||01 - Articolo su rivista|