Deregulation of TWIST-1 in the CD34+ compartment represents a novel prognostic factor in chronic myeloid leukemia.

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.

journal_name

Blood

journal_title

Blood

authors

Cosset E,Hamdan G,Jeanpierre S,Voeltzel T,Sagorny K,Hayette S,Mahon FX,Dumontet C,Puisieux A,Nicolini FE,Maguer-Satta V

doi

10.1182/blood-2009-11-254680

subject

Has Abstract

pub_date

2011-02-03 00:00:00

pages

1673-6

issue

5

eissn

0006-4971

issn

1528-0020

pii

blood-2009-11-254680

journal_volume

117

pub_type

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