VEGA 2/0122/17


Study of changes in expression of some regulatory and functional proteins connected with the presence of P-gp protein in leukemic cells      

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Principal investigator: Zdena Sulova

Duration: January 2017 – December 2020

Coordinating institution: Institute of Molecular Physiology and Genetics, SAS, Bratislava


Successful treatment of hematologic malignancies depends on the efficacy of chemotherapy. The P-glycoprotein (P-gp) overexpression is one of the most common causes of multidrug resistance (MDR) in leukemic cells. The presence of this protein in human and murine cell lines leads not only to resistance against P-gp substrates but significant is also its influence on cell response to substrates, which are not P-gp substrates. In our work, we found that P-gp expression in this cells was accompanied by changes in the levels/activities of regulatory or structural proteins. Some of these proteins are involved in the regulation pathway of apoptosis (Bcl-2 family proteins) or they can be the target of leukemia immunotherapy (CD33). The solving of this project have the potential to bring results clinically applicable in therapeutic protocols aimed to appropriate type of neoplastic diseases.


resistant leukemia, P-glycoprotein, regulation of apoptosis, regulatory and functional proteins


Aims of this project are subjected to the detailed study of changes in the important cellular regulatory pathways, connected with the presence of P-gp in the leukemia cell line L1210, SKM-1 and MOLM-13 etc., which we have detected in the past. To achieve these aims, we will focus particularly on:

  • Comparison of changes in expression/glycosylation and localization of membrane proteins associated with P-gp expression in murine and human leukemia cells.
  • Influence of the presence of substances inducing stress of endoplasmic reticulum on sensitive and resistant leukemic cell sublines. Analysis of the changes in endoplasmic reticulum ultrastructure using electron microscopy.
  • Study of changes in progression of appropriate type of cell death after induction with compounds that are not substrates of P-gp in leukemia cells expressing and non-expressing P-gp. Monitoring the levels and localization of pro- and anti-apoptotic proteins.
  • Monitoring of protein phosphorylation using radioactive phosphate in the presence of kinase inhibitors. Comparison of differences in the effect of substances on the protein phosphorylation in P-gp positive and negative human and murine leukemia cells.
  • Study of co-expression of regulatory and functional proteins with P-gp in leukemia cells.