title: Phenotypic and genotypic characterization of azacitidine-sensitive and resistant SKM1 myeloid cell lines.
abstract: 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.
authors: INSERM U1065, Mediterranean Center for Molecular Medicine (C3M), Nice, France; University of Nice, Nice, France.
authors: Thomas
authors: T
authors: Cluzeau
authors: Alix
authors: A
authors: Dubois
authors: Arnaud
authors: A
authors: Jacquel
authors: Frederic
authors: F
authors: Luciano
authors: Aline
authors: A
authors: Renneville
authors: Claude
authors: C
authors: Preudhomme
authors: Jean Michel
authors: JM
authors: Karsenti
authors: Nicolas
authors: N
authors: Mounier
authors: Pierre
authors: P
authors: Rohrlich
authors: Sophie
authors: S
authors: Raynaud
authors: Bernard
authors: B
authors: Mari
authors: Guillaume
authors: G
authors: Robert
authors: INSERM U1065, Mediterranean Center for Molecular Medicine (C3M), Nice, France; University of Nice, Nice, France; Department of Clinical hematology and Transplantation, CHU of Nice, Nice, France.
authors: Patrick
authors: P
authors: Auberger
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D001374:Azacitidine / Q000494:pharmacology*; D045744:Cell Line, Tumor; D015536:Down-Regulation; D005838:Genotype; D006801:Humans; D009190:Myelodysplastic Syndromes / Q000378:metabolism* / Q000473:pathology; D022423:Myeloid Cells / Q000187:drug effects* / Q000502:physiology; D010641:Phenotype
chemical_list: D000964:Antimetabolites, Antineoplastic; D001374:Azacitidine