Genomic and transcriptomic profiling of resistant CEM/ADR-5000 and sensitive CCRF-CEM leukaemia cells for unravelling the full complexity of multi-factorial multidrug resistance

AbstractWe systematically characterised multifactorial multidrug resistance (MDR) in CEM/ADR5000 cells, a doxorubicin-resistant sub-line derived from drug-sensitive, parental CCRF-CEM cells developed in vitro. RNA sequencing and network analyses (Ingenuity Pathway Analysis) were performed. Chromosomal aberrations were identified by array-comparative genomic hybridisation (aCGH) and multicolour fluorescence in situ hybridisation (mFISH). Fifteen ATP-binding cassette transporters and numerous new genes were overexpressed in CEM/ADR5000 cells. The basic karyotype in CCRF-CEM cells consisted of 47, XX, der(5)t(5;14) (q35.33;q32.3), del(9) (p14.1), +20. CEM/ADR5000 cells acquired additional aber…