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- Deregulation of TWIST-1 in the CD34+ compartment represents a novel prognostic factor in chronic myeloid leukemia
Deregulation of TWIST-1 in the CD34+ compartment represents a novel prognostic factor in chronic myeloid leukemia
Authors
Erika Cosset, Ghassan Hamdan, Sandrine Jeanpierre, Thibault Voeltzel, Karen Sagorny, Sandrine Hayette, François-Xavier Mahon, Charles Dumontet, Alain Puisieux, Franck E. Nicolini, Véronique Maguer-Satta
Abstract
Abstract
The mechanisms of resistance to tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML) often remain obscure. Analysis of patient samples during disease progression revealed the up-regulation of the oncogene TWIST-1, also measured in primary samples from TKI-resistant patients. Moreover, we found that TWIST-1 was overexpressed in CML diagnostic samples of patients who later developed cytogenetic resistance to imatinib, even those without any detectable resistance mechanism. We confirmed the up-regulation of TWIST-1 at both RNA and protein levels in imatinib-resistant cell lines, irrespective of any other resistance mechanism. Analysis with specific small interfering RNA suggested TWIST-1 involvement in the resistance phenotype. Finally, the kinetics of TWIST-1 expression during the individual medical histories of CML patients indicated that TWIST-1 expression is down-regulated by TKIs and up-regulated with TKI resistance. We hypothesize that the overexpression of the TWIST-1 oncogene represents a novel key prognostic factor potentially useful for optimizing CML management in the TKI era.