Kajetana Foryciarz

Publications of Kajetana Foryciarz

• [H-oCT1 gene expression as a predictor of major and complete molecular response to imatinib of chronic myeloid leukemia. Single center experience].

  Authors: Tomasz Sacha, Sylwia Czekalska, Kajetana Foryciarz, Magdalena Zawada, Izabela Florek, Dorota Cwynar, Gracjan Wator, Walentyna Balwierz, Aleksander B Skotnicki

  Przegla̧d lekarski. 01/2011; 68(4):191-5.

  Chronic myeloid leukemia is a clonal disorder caused by formation of chimeric BCR/ABL gene and bcr/abl protein with abnormally high tyrosine kinase activity. The use of imatinib--the first tyrosineChronic myeloid leukemia is a clonal disorder caused by formation of chimeric BCR/ABL gene and bcr/abl protein with abnormally high tyrosine kinase activity. The use of imatinib--the first tyrosine kinase inhibitor results in achievement of hematologic, cytogenetic and molecular response in majority of patients. However despite its high efficacy not all patients respond to imatinib, whereas others lose an initial response. Imatinib is a substrate of human organic cation transporter-1 (hOCT1), which actively delivers the drug into the cells, and efflux transporters. To identify potential imatinib failures, we investigated the expression of hOCT1 using real-time quantitative reverse transcription-polymerase chain reaction (RQ-PCR) in 155 CML patients. Patients with low pretreatment hOCT1 expression had inferior major and complete molecular response (MMR and CMR) rates (p = 0.0001, p = 0.0001) achieved any time or at 18 months of imatinib treatment (p = 0.023, p = 0.022). The expression of hOCT1 is important in determining the clinical response to imatinib. The analysis of hOCT1 expression by RQ-PCR is convenient and clinically available, and the results could help in introduction of optimal first line therapy in CML patients.

• [ABL domain kinase point mutations as a cause of resistance to therapy of patients with chronic myeloid leukemia with tyrosine kinase inhibitors. Single center experience].

  Authors: Tomasz Sacha, Kajetana Foryciarz, Izabela Florek, Magdalena Zawada, Sylwia Czekalska, Dorota Cwynar, Elzbieta Pecek, Aleksander B Skotnicki

  Przegla̧d lekarski. 01/2011; 68(5):253-7.

  Introduction of tyrosine kinase inhibitors (TKIs) in the therapy of chronic myeloid leukemia have been significantly improved the results of the treatment and prognosis of CML patients. Despite ofIntroduction of tyrosine kinase inhibitors (TKIs) in the therapy of chronic myeloid leukemia have been significantly improved the results of the treatment and prognosis of CML patients. Despite of high efficacy of TKIs therapy, resistance is developing in substantial percentage of patients, which accounts for up to 40% after several years of treatment. There are several identified mechanisms of resistance to TKIs. The presence of ABL kinase domain point mutation, which could be detected by molecular methods is one of them. The aim of the study was to screen 60 CML patients resistant to TKI therapy for the presence of ABL point mutation. ABL mutation was detected in 19 (31,6%) patients. In four cases with detected mutation the disease has progressed to blast crisis. Investigation of ABL mutation occurrence can help in finding the cause of resistance to TKI therapy in some patients suffering from CML.

• [Implementation of direct sequencing as a method of ABL gene mutations analysis in patients with chronic myeloid leukemia treated with tyrosine kinase inhibitor].

  Authors: Izabela Florek, Tomasz Sacha, Magdalena Zawada, Sylwia Czekalska, Kajetana Foryciarz, Dorota Cwynar, Elzbieta Pecek, Aleksander B Skotnicki

  Przegla̧d lekarski. 01/2010; 67(12):1292-7.

  Chronic Myeloid Leukemia (CML), belonging to mieloproliferative syndromes, is one of the myeloproliferative clonal hyperplasia. It is caused by the Philadelphia chromosome resulting from theChronic Myeloid Leukemia (CML), belonging to mieloproliferative syndromes, is one of the myeloproliferative clonal hyperplasia. It is caused by the Philadelphia chromosome resulting from the reciprocal translocation, t(9;22) between the long arms of chromosomes 9 and 22. This results in the production of fusion BCR-ABL transcript and chimeric protein--tyrosine kinase activity. This protein leads to increased proliferation, resistance to apoptosis, and worse adhesion of CML cells. Molecular analysis are very important in the era treatment of CML by tyrosine kinase inhibitors (TKI). Constant monitoring of the level of BCR-ABL transcript aimed at monitoring response to medical treatment as well as early detection of resistance to TKI therapy. The most common causes of resistance are point mutations ABL kinase domain of the BCR-ABL gene. In this aim, the biological material used (peripheral blood) derived from 58 patients of the Department of Hematology, Jagiellonian University Collegium Medicum. The isolated RNA was performed in successive stages: RT-PCR, RQ-PCR to a semi-nested PCR. In order to detect point mutations ABL kinase domain technique used direct sequencing of the product obtained in response to a semi-nested PCR. Using this technique allow in do not only a rapid detection of point mutations but also identification of its position in the ABL domain, type of mutation (e.g., T3151), as well as nucleotide and the amino acid substitution. The most common point mutations detected were T3151 and M244V.

• Frequency of BCR-ABL gene mutations in Polish patients with chronic myeloid leukemia treated with imatinib: a final report of the MAPTEST study.

  Authors: Krzysztof Lewandowski, Krzysztof Warzocha, Andrzej Hellmann, Aleksander Skotnicki, Witold Prejzner, Kajetana Foryciarz, Tomasz Sacha, Michał Gniot, Mirosław Majewski, Iwona Solarska, Grazyna Nowak, Bartosz Wasag, Mikołaj Kobelski, Cezary Scibiorski, Marek Siemiatkowski, Maria Lewandowska, Mieczysław Komarnicki

  Polskie archiwum medycyny wewnȩtrznej. 12/2009; 119(12):789-94.

  INTRODUCTION: The presence of BCR-ABL oncogene mutations in patients with chronic myeloid leukemia (CML) may be responsible for the failure of tyrosine kinase inhibitor treatment. OBJECTIVES: The aimINTRODUCTION: The presence of BCR-ABL oncogene mutations in patients with chronic myeloid leukemia (CML) may be responsible for the failure of tyrosine kinase inhibitor treatment. OBJECTIVES: The aim of the study was to evaluate the frequency of BCR-ABL gene mutations in patients with CML (the MAPTEST study) treated with imatinib (IM). PATIENTS AND METHODS: Direct sequencing analysis of BCR-ABL gene was performed in 92 patients treated with IM for more than 3 months. The mean time of IM treatment was 18 months. At the time of the analysis, 75 patients were in the first chronic phase (CP), 4 in the second CP, 5 in the acceleration and 8 in the blastic phase. Fifty-seven patients (62%) were treated with IM at a daily dose of 400 mg and 35 patients with higher doses (600 or 800 mg daily). Inclusion criteria were based on the European Leukemia Net definitions for failure and suboptimal response to IM. RESULTS: Twelve mutations were detected in 11 of 92 patients, including 4 mutations (36.7%) diagnosed during CP, 3 (27.3%) in acceleration, and 4 (36.7%) in blast crisis. In 1 patient with lymphoid blast crisis of CML coexisting F359V and Y253F mutations were detected. In the whole group mutations were detected in 2 of 5 patients (40%) with primary resistance (M351T, F359V + Y253F) and in 9 of 87 patients (10.3%) (E255K, T315I-3x, M351T, E355G, F359V-2x) with acquired resistance to IM. CONCLUSIONS: The study confirmed the usefulness of BCR-ABL gene mutation screening in patients with CML resistant to IM therapy.

• [Angiogenesis in different clinical phases of chronic myeloid leukemia].

  Authors: Aleksandra Krasowska-Kwiecień, Jacek Kijowski, Ewa Łukasiewicz, Tomasz Sacha, Kajetana Foryciarz, Marcin Majka, Mariusz Z Ratajczak, Aleksander B Skotnicki

  Przegla̧d lekarski. 01/2009; 66(9):471-8.

  Angiogensis plays the crucial role in growth and dissemination of neoplastic diseases, both for solid tumors and hematopoietic malignancies. Development of the abundant neoplastic vasculature resultsAngiogensis plays the crucial role in growth and dissemination of neoplastic diseases, both for solid tumors and hematopoietic malignancies. Development of the abundant neoplastic vasculature results from an imbalance between pro- and antiangiogenic regulatory mechanisms. The investigation was focused on expression of the main regulatory angiogeneic factors in different phases of chronic myeloid leukemia (CML) and on influence of leukemic cells on the human umbilical vein endothelial cells proliferation. The groups of 29 patients with CML and of 14 healthy controls were enrolled to the study. The expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor, interleukin-8, angiopoetin-1, platelet factor-4, extracellular matrix metalloproteinases (MMP) -2 and -9 as well as tissue inhibitors of metalloproteinases was determined in peripheral blood and bone marrow mononuclear cells with the use of quantitative real-time PCR method and additionally the concentration of VEGF with the flow cytofluorometry. We evaluated the phosphorylation of endothelial mitogen activated protein kinase in human umbilical vein endothelial cells after incubation in CML cells conditioned media, applying Western blot technique. We determined an influence of the leukemic cells on the endothelial cells proliferation with the colorimetric metabolic MTT test. We showed, that in peripheral blood and bone marrow mononuclear cells in CML patients most of the studied factors were increased at the time of CML diagnosis and became lower in remission. In newly diagnosed CML patients an expression of VEGF, MMP-2 and MMP-9 was particularly elevated. In remission, the levels of VEGF and metalloproteinases, specifically MMP-9, were decreased. If failed to achieve remission, the patients presented the elevated expression of most of the investigated angiogenic factors. In the acceleration or blast crisis phase angiopoetin, VEGF and MMP-2 levels were particularly high. We noticed the markedly enhanced human umbilical vein endothelium proliferation after an incubation in CML cells conditioned media, both in the test of mitogen activated protein kinase phosphorylation in endothelial cells and in the metabolic test for the proliferation intensity of endothelium. The differences of an angiogeneic potential found between clinical phases of CML, and the ability of leukemic cells to stimulate endothelial proliferation, point at the significance of neovascularisation in CML pathogenesis. Further studies are necessary to delineate the possibility of the use of angiogenic inhibitors in the treatment of this malignancy.