General AML

The expression of P-glycoprotein in leukemia cells is associated with the upregulated expression of nestin, a class 6 filament protein

Coculova M, et al., analyzed whether there was correlation between the expression of P-glycoprotein and the expression of nestin in Acute Myeloid Leukemia (AML) cell lines (SKM-1 and MOLM-13). The study is of interest as the findings could further elucidate the mechanisms by which Multidrug Resistance (MDR) occurs during chemotherapy treatment. The data were published in Leukemia Research in July 2016.

The key findings were:
  • Co-expression of P-glycoprotein and nestin in AML cell lines was detected
  • Silencing the P-glycoprotein induced the downregulation of nestin
  • Nestin expression in L1210 cells transfected with P-glycoprotein gene was observed

In conclusion, a causal relationship was observed between expression of P-glycoprotein and the expression of nestin in AML cell lines. This data suggests that the targeting of the P-glycoprotein could provide a mode of preventing multiple drug resistance to chemotherapy agents used to treat leukemia.

The expression of P-glycoprotein in leukemia cells is associated with the upregulated expression of nestin, a class 6 filament protein.

Abstract

Multidrug resistance (MDR) is a serious obstacle to the effective chemotherapeutic treatment of leukemia. Expression of plasma membrane P-glycoprotein (P-gp), a transporter involved in drug efflux, is the most frequently observed molecular causality of MDR. We observed the coexpression of P-gp and the filament protein nestin in the acute myeloid leukemia (AML) cell lines SKM-1 and MOLM-13 following the induction of P-gp expression using vincristine. Nestin is considered a marker of neural stem cells and neural progenitor cells. The aim of this study was to determine whether there is causal relationship between the expression of P-glycoprotein and the expression of nestin in both of these AML cell lines. The expression of P-gp was induced in SKM-1 cells by selective pressure using vincristine (VCR), mitoxantrone (MTX), azacytidine (AzaC) and lenalidomide (LEN). Whereas the selective pressure of VCR, MTX and AzaC also induced P-gp expression in MOLM-13 cells, LEN was found to be ineffective in this regard. In all cases in which P-gp expression was induced in SKM-1 and MOLM-13 cells, its expression was associated with the induction of nestin mRNA expression and the presence of a 200-220kDa nestin-immunoreactive protein band in western blots. Silencing P-gp expression using s10418 siRNA (known as the P-gp silencer) was associated with the downregulation of the nestin transcript level, demonstrated using RT-PCR. Nestin mRNA was also observed in two P-gp-positive variants of L1210 cells that were obtained either by selection with VCR or by transfection with a retrovirus encoding human P-gp. Detectable levels of nestin transcripts were not observed in P-gp-negative parental L1210 cells. Taken together, these results indicated that the induction of P-gp expression is causally associated with the expression of nestin in leukemia cells.

References
  1. Coculova M, et al. The expression of P-glycoprotein in leukemia cells is associated with the upregulated expression of nestin, a class 6 filament protein. Leuk Res. 2016 Jul 21; 48:32–39. DOI: 10.1016/j.leukres.2016.05.021. [Epub ahead of print].