Phenotypic and genotypic characterization of azacitidine-sensitive and resistant SKM1 myeloid cell lines
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Thomas Cluzeau1,2,3,4,6,*, Alix Dubois1,2,3,4,*, Arnaud Jacquel1,2,3,4, Frederic Luciano1,2,3,4, Aline Renneville5, Claude Preudhomme5, Jean Michel Karsenti6, Nicolas Mounier6, Pierre Rohrlich6, Sophie Raynaud7, Bernard Mari8, Guillaume Robert1,2,3,4 and Patrick Auberger1,2,3,4,6
1 INSERM U1065, Mediterranean Center for Molecular Medicine (C3M), Nice, France
2 INSERM U1065, Team 2: Cell Death, Differentiation, Inflammation and Cancer
3 Equipe labellisée par la Ligue Nationale Contre le Cancer (2011-2013), Paris, France
4 University of Nice, Nice, France
5 Laboratory of Hematology, Biology and Pathology Center, CHRU of Lille, Lille, France
6 Department of Clinical hematology and Transplantation, CHU of Nice, Nice, France
7 Oncohematology laboratory, CHU of Nice, Nice, France
8 Molecular and Cellular Pharmacology Institute, CNRS, Sophia-Antipolis, France
* These authors participated equally to this work
Patrick Auberger, email:
Keywords: MDS, AML, Azacitidine, Polyploidy, TET2, ASLX1
Received: May 5, 2014 Accepted: May 26, 2014 Published: May 27, 2014
In the present study, we provide a comparative phenotypic and genotypic analysis of azacitidine-sensitive and resistant SKM-1 cell lines. Morphologically, SKM1-R exhibited increase in cell size that accounts for by enhanced ploidy in a majority of cells as shown by cell cycle and karyotype analysis. No specific Single Nucleotide Polymorphism (SNP) alteration was found in SKM1-R cells compared to their SKM1-S counterpart. Comparative pangenomic profiling revealed the up-regulation of a panel of genes involved in cellular movement, cell death and survival and down-regulation of genes required for cell to cell signaling and free radical scavenging in SKM1-R cells. We also searched for mutations frequently associated with myelodysplastic syndromes (MDS) and found that both cell lines harbored mutations in TET2, ASLX1 and TP53. Collectively, our data show that despite their different morphological and phenotypic features, SKM1-S and SKM1-R cells exhibited similar genotypic characteristics. Finally, pangenomic profiling identifies new potential pathways to be targeted to circumvent AZA-resistance. In conclusion, SKM1-R cells represent a valuable tool for the validation of new therapeutic intervention in MDS.
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