title: Dendrimer-based nanoparticles for potential personalized therapy in chronic lymphocytic leukemia: Targeting the BCR-signaling pathway.
abstract: Chronic lymphocytic leukemia (CLL) is one of the most prevalent forms of leukemia in western society. Although classic chemoimmune therapy is still the gold standard of care for leukemic patients, effective therapy of CLL is yet to be achieved. The present study examines the influence of poly(propylene)imine (PPI) dendrimers with primary amino surface groups modified with maltotriose residues in approximately 90% (PPI-G4-DS-Mal-III) or 30% (PPI-G4-OS-Mal-III) of cases on CLL cells (MEC-1 cell line with del(17p)), and confirms that the main trigger in this interaction is the induction of the apoptotic mechanism. The efficacy of each dendrimer was compared using fludarabine (FA). Gene expression profiling (GEP) by microarray identified a group of genes in the BCR signaling pathway characterized by different levels of expression directly associated with the tested agent and type of interaction. Network analysis revealed the potential patterns involved in potential personalized therapy of CLL. The expression of most BCR genes decreased under the influence of dendrimers, which might translate into decreased maturation and proliferation of CLL lymphocytes. Moreover, PPI-G4-OS/DS-Mal-III dendrimers affected gene expression and CLL cells in a different way to FA. Thanks to unique properties, dendrimers may be specifically targeted, thus improving the effectiveness of CLL therapy.
authors.affiliation: Department of Clinical and Laboratory Genetics, Medical University of Lodz, Poland; Laboratory of Clinical and Transplant Immunology and Genetics, Copernicus Memorial Hospital, Poland. Electronic address: ida.fp@interia.pl.
authors.forename: Ida
authors.initials: I
authors.lastname: Franiak-Pietryga
authors.affiliation: Department of Computer Engineering, Wroclaw University of Technology, Wroclaw, Poland.
authors.forename: Henryk
authors.initials: H
authors.lastname: Maciejewski
authors.affiliation: Laboratory of Clinical and Transplant Immunology and Genetics, Copernicus Memorial Hospital, Poland; Department of Immunobiology of Bacteria, Faculty of Biology and Environmental Protection, University of Lodz, Poland.
authors.forename: Kinga
authors.initials: K
authors.lastname: Ostrowska
authors.affiliation: Leibniz Institute of Polymer Research Dresden, Dresden, Germany.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Appelhans
authors.affiliation: Leibniz Institute of Polymer Research Dresden, Dresden, Germany.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Voit
authors.affiliation: Department of Hematology, Medical University of Lodz, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Misiewicz
authors.affiliation: Bionicum Ltd., Warsaw, Poland.
authors.forename: Paweł
authors.initials: P
authors.lastname: Kowalczyk
authors.affiliation: Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Poland.
authors.forename: Maria
authors.initials: M
authors.lastname: Bryszewska
authors.affiliation: Department of Clinical and Laboratory Genetics, Medical University of Lodz, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Borowiec
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D001402:B-Lymphocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D001483:Base Sequence; D045744:Cell Line, Tumor; D002886:Chromosomes, Human, Pair 17; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D046228:Microarray Analysis; D058990:Molecular Targeted Therapy; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D011126:Polypropylenes / Q000737:chemistry* / Q000378:metabolism; D057285:Precision Medicine; D051562:Proto-Oncogene Proteins c-bcr / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D017384:Sequence Deletion; D015398:Signal Transduction; D014312:Trisaccharides / Q000737:chemistry; D014740:Vidarabine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D011126:Polypropylenes; D014312:Trisaccharides; C443641:poly(propyleneimine); C008317:maltotriose; C496613:BCR protein, human; D051562:Proto-Oncogene Proteins c-bcr; D014740:Vidarabine; C024352:fludarabine
keywords: B-cell receptor (BCR); Chronic lymphocytic leukemia (CLL); Gene expression; Poly(propylene imine)dendrimers (PPI)