Efficacy of cancer chemotherapy may be impaired by tumor resistance to multiple, structurally unrelated therapeutic drugs with different mechanisms of action, a phenomenon termed multidrug resistance (MDR). One mechanism of MDR is decreased intracellular drug accumulation resulting from expression of the ATP-dependent drug efflux transporter P-glycoprotein (P-gp, ABCB1) or related ATP-binding cassette (ABC) transporters, including the recently identified novel P-gp family member ABCB5. ABCB5 regulates membrane potential and cell fusion of skin progenitor cells and mediates resistance to doxorubicin, 5-FU and camptothecin in human malignant melanoma in cells of cancer stem cell (CSC) phenotype and function. Relatively little is known regarding the expression and function of the ABCB5 gene in additional physiological and malignant tissues. In this issue of Leukemia Research, Lehne et al. report ABCB5 gene amplification and enhanced ABCB5 gene expression in multidrug resistant human K562 leukemia cells. Intriguingly, upregulated expression of the CSC marker ABCB5 is associated with en bloc activation of hematopoietic and leukemic stem cell genes, indicating that ABCB5 might represent a chemoresistance mechanism in leukemic stem cells.

In order to identify genes associated with multidrug resistance acquired by human K562 chronic myelogenous leukemia (CML) cells through vincristine (VCR) selection, Lehne et al. performed comparative genomic hybridization (CGH) and gene expression profiling of drug resistant K562VCR cells compared to sensitive wildtype (wt) K562wt cultures. CGH revealed amplification of the human ABC transporter genes ABCB1, ABCB4 and ABCB5 in K562VCR compared to K562wt cells, and these gene amplifications were associated with overexpression of the respective mRNAs in resistant K562VCR cells. In addition, expression microarrays demonstrated upregulation of stem cell genes (eg KIT, HOXB4) and anti-apoptotic genes (eg IGF1R, CCNG1), as well as downregulation of pro-apoptotic genes (eg CASP4, 6 and 7) in