POTENTIAL GENETIC AGENT BFL1 FOR TARGETED THERAPY IN CHRONIC LYMPHOCYTIC LEUKEMIA

  • Ida Franiak-Pietryga Department of Clinical and Laboratory Genetics, Medical University of Lodz, Poland
  • Bogusław Tymoniuk Department of Clinical and Laboratory Genetics, Medical University of Lodz, Poland
  • Maciej Borowiec Department of Clinical and Laboratory Genetics, Medical University of Lodz, Poland
  • Ewelina Ziolkowska Department of Hematology, Medical University of Lodz, Poland
  • Jerzy Z. Blonski Department of Hematology, Medical University of Lodz, Poland
  • Agnieszka Janus Department of Hematology, Medical University of Lodz, Poland
  • Malgorzata Misiewicz Department of Hematology, Medical University of Lodz, Poland
  • Ewa Wawrzyniak Department of Hematology, Medical University of Lodz, Poland
  • Jacek Trelinski Department of Hematology, Medical University of Lodz, Poland
  • Tadeusz Robak Department of Hematology, Medical University of Lodz, Poland
  • Henryk Maciejewski Institute of Computer Engineering, Control and Robotics I-6, Wroclaw University of Technology, Poland
  • Ryszard Tomasiuk Brodno Voivodship Hospital, Biochemistry Laboratory, Warsaw, Poland
  • Barbara Cebula-Obrzut Department of Experimental Hematology, Medical University of Lodz, Poland
  • Piotr Smolewski Department of Experimental Hematology, Medical University of Lodz, Poland
  • Joanna Kaminska Laboratory of Clinical and Transplant Immunology and Genetics, Copernicus Memorial Hospital, Lodz, Poland
  • Anna Stępien Laboratory of Clinical and Transplant Immunology and Genetics, Copernicus Memorial Hospital, Lodz, Poland
  • Marek Mirowski Department of Pharmaceutical Biochemistry, Laboratory of Molecular Diagnostics and Pharmacogenomics, Medical University of Lodz, Poland
  • Joanna Gora-Tybor Hematology and Transfusiology Institute, Warsaw, Poland

Abstract

Background: Many prognostic factors have been identified in chronic lymphocytic leukemia (CLL) but new ones are still desired. The biological characterization of CLL is now being translated into novel treatment strategies. One new prognostic factor, and therapeutic target, may be BFL1. It is both a serum and a molecular marker that contributes to the progression of CLL and its resistance to chemotherapy. The aim of this study was to evaluate the prognostic value of BFL1 and to assess its correlation with other known prognostic markers in CLL for the cladribine and cyclophosphamide regimen (CC). Methods: qPCR TaqMan® Low Density Array was used for gene expression measurements. Assessment of CD38, ZAP70 and BFL-1 proteins expression was done by means of flow cytometry. Serum TK activity was measured by immunoassay. Results: Protein BFL1 expression was found to be significantly higher in CLL patients than healthy volunteers (p=0.001). Moreover its level was significantly higher in patients with no response (NR) to CC therapy (p=0.009). The expression of BFL1 was considerably down regulated during CC treatment and BFL1 mRNA levels were inversely correlated with apoptotic response. In addition, protein BFL1 expression was found to be similar to thymidine kinase (TK) concentration regarding treatment response. As far as other markers are concerned, a positive correlation was identified between BFL1 and TK (r=0.52, p=0.01). Conclusions: Our findings suggest that BFL1 contributes to chemoresistance and may be a co-existing prognostic factor in CLL in the future.

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Published
2015-09-29
How to Cite
Franiak-Pietryga, I., Tymoniuk, B., Borowiec, M., Ziolkowska, E., Blonski, J. Z., Janus, A., Misiewicz, M., Wawrzyniak, E., Trelinski, J., Robak, T., Maciejewski, H., Tomasiuk, R., Cebula-Obrzut, B., Smolewski, P., Kaminska, J., Stępien, A., Mirowski, M., & Gora-Tybor, J. (2015). POTENTIAL GENETIC AGENT BFL1 FOR TARGETED THERAPY IN CHRONIC LYMPHOCYTIC LEUKEMIA. European Scientific Journal, ESJ, 11(27). Retrieved from https://eujournal.org/index.php/esj/article/view/6272