Tomasz Sacha
Research interests
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InterestsClinical Laboratory Techniques, Clinical Laboratory, Clinical Hematology, Clinical Oncology
Publications
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[H-oCT1 gene expression as a predictor of major and complete molecular response to imatinib of chronic myeloid leukemia. Single center experience].
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 tyrosine kinase inhibitor results in achievement of hematologic, cytogenetic and molecular response in majority... [more] 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 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.
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[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].
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 of high efficacy of TKIs therapy, resistance is developing in substantial percentage of patients, which ac... [more] 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 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.
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[Beta-carotene regulates the expression of proapoptotic BAX and CAPN2 in HL-60, U-937 and TF-1 - human acute myeloid leukemia cell lines; microarray, RQ-PCR and Western Blot analysis].
Przegla̧d lekarski. 01/2011; 68(5):258-62.
Beta carotene (BC) is a nutritional compound widespread in foods which can influence vital cellular functions--differentiation, proliferation and apoptosis of normal and cancer cells. However its role in the carcinogenesis remains controversial. We performed a microarray expression analysis in three... [more] Beta carotene (BC) is a nutritional compound widespread in foods which can influence vital cellular functions--differentiation, proliferation and apoptosis of normal and cancer cells. However its role in the carcinogenesis remains controversial. We performed a microarray expression analysis in three human acute leukemia cell lines (HL-60, U937 and TF-1) exposed to 10mM BC and found that BC stimulated the apoptosis in all studied cell lines. This effect was most evident in the HL-60 cell line and correlated with increased expression of proapoptotic BAX and CAPN2 genes. The micro-array findings were replicated by the quantitative BAX and CAPN2 expression analysis using real-time PCR and by Western Blot on protein level. The biological tests (TUNEL method) for apoptosis showed consistent proapoptotic effects in all studied cell lines. In this paper the stimulatory effect of BC on apoptosis (enhanced expression of proapoptotic genes and proteins) in human acute myeloid leukemia cells was confirmed. The most potent activation of apoptosis in the HL-60 cells is in line with other investigators observations suggesting distinct molecular mechanism of apoptosis stimulation by BC in different human acute myeloid leukemia cells.
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[Implementation of direct sequencing as a method of ABL gene mutations analysis in patients with chronic myeloid leukemia treated with tyrosine kinase inhibitor].
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 the reciprocal translocation, t(9;22) between the long arms of chromosomes 9 and 22. This results in the producti... [more] Chronic 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.
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[Evaluation of hematopoietic chimerism after allogeneic bone marrow transplantation by modern molecular techniques (STR-PCR and RQ-PCR)--single center].
Przegla̧d lekarski. 01/2010; 67(12):1282-91.
Allogeneic hematopoietic stem cell transplantation (alloSCT) is a curative treatment for many patients suffering from malignant and non-malignant hematological disorders. Successful transplantation is a process that requires the engraftment of transplanted pluripotent hematopoietic stem cells which ... [more] Allogeneic hematopoietic stem cell transplantation (alloSCT) is a curative treatment for many patients suffering from malignant and non-malignant hematological disorders. Successful transplantation is a process that requires the engraftment of transplanted pluripotent hematopoietic stem cells which re-establish normal hematological and immunological systems. Distinguishing between host and donor origin of bone marrow and blood cells is vitally important for monitoring of the engraftment process. One of the most useful tools for engraftment monitoring is the assessment of hematopoietic chimerism. Which occurs after alloHSCT and describes the percentage of donor hematopoietic and lymphoid cells in a transplant recipient. 38 adult patients, after alloSCT performed in Katedra i Klinika Hematologii Collegium Medicum UJ entered the study and the total number of transplantations was 43. The evaluation of hematopoietic chimerism was based on PCR amplification of polymorphic non-coding DNA sequences--short tandem repeats (STR-PCR). The main tool was a semiquantitative method--fragment length analysis. The product of amplification was analyzed using the sequencer. The second method was based on a quantitative Real Time PCR technique (RQ-PCR) based on SYBRgreen chemistry. There were performed amplification of biallelic non-coding DNA sequences with short insertions or deletions. Hematopoietic chimerism evaluations were performed on +30, +60, +90, +120, +150, +180, +270 and +360 day and then every 6 months post alloSCT on peripheral blood or bone marrow samples. STR-PCR and RQ-PCR chimerism assays were compared and results evidenced the greater sensitivity of RQ-PCR method. There were not crucial differences in the results of chimerism evaluation obtained by means of these two methods. The analysis of chimerism kinetics after allogeneic stem cell transplantation allowed to modify the post-transplantation-treatment in 3 patients after alloNMSCT leading to increase of donor-origin hematopoiesis in transplant recipients (in 2 pts decision of DLI, 1 of them withdrawal of immunosuppression, 1 pt giving G-CSF). The results of chimerism monitoring confirmed that the failure of achieving a CC or lost of CC can predict the relapse of the disease.
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[Standardization of quantitative detection of BCR-ABL gene expression by RQ-PCR in patients with chronic myeloid leukemia in cooperation with European Leukemia Net].
Przegla̧d lekarski. 01/2010; 67(7):454-9.
Monitoring of chronic myeloid leukemia treatment efficacy requires very sensitive methods of BCR-ABL gene detection based on polymerase chain reaction (PCR). The lack of comparability of BCR-ABL mRNA quantification results generated by various methodologies in different laboratories was the cause of... [more] Monitoring of chronic myeloid leukemia treatment efficacy requires very sensitive methods of BCR-ABL gene detection based on polymerase chain reaction (PCR). The lack of comparability of BCR-ABL mRNA quantification results generated by various methodologies in different laboratories was the cause of an international multicenter trial initiation with the participation of 133 laboratories in 24 European countries cooperating within the "EUTOS for CML" project. Pracownia Diagnostyki Molekularnej Kliniki Hematologii is taking part in standardisation rounds organised since 2005. The compatibility of methodology used in Pracownia with European Leukemia Net (ELN) standards was confirmed, and correction factor for the expression of RQ-PCR results in an international scale was calculated. Pracownia was charge by ELN with a task of conducting the standardisation in polish molecular biology laboratories. Test probes were prepared and sent to eight cooperating laboratories. The results obtained in six laboratories were concordant with results from laboratory in Krakow after conversion to international scale, therefore it was possible to calculate individual correction factors. The participation of polish laboratories in international standardization process created the opportunity for unification of BCR-ABL quantification methodologies with recommendations of international experts, and showed that the quality of analyses performed in majority of them was satisfactory enough to calculate correction factor and to express the RQ-PCR results in widely accepted international scale.
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Frequency of BCR-ABL gene mutations in Polish patients with chronic myeloid leukemia treated with imatinib: a final report of the MAPTEST study.
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 aim of the study was to evaluate the frequency of BCR-ABL gene mutations in patients with CML (the MAPTE... [more] 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 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.
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2.40Impact points
Wilms' tumor gene 1 expression analysis by real-time quantitative polymerase chain reaction for monitoring of minimal residual disease in acute leukemia.
Leukemia & lymphoma. 08/2009; 50(8):1326-32.
Wilms' tumor gene 1 (WT1) gene expression was analyzed in 32 patient with acute myeloid leukemia (AML) and 18 with acute lymphoblastic leukemia (ALL) to investigate whether it could serve as a MRD marker. Ninety-four percent of patients with acute leukemia showed high WT1 expression at presentat... [more] Wilms' tumor gene 1 (WT1) gene expression was analyzed in 32 patient with acute myeloid leukemia (AML) and 18 with acute lymphoblastic leukemia (ALL) to investigate whether it could serve as a MRD marker. Ninety-four percent of patients with acute leukemia showed high WT1 expression at presentation. WT1 expression as a MRD marker was evaluated in 36 patients. The rise of WT1 expression preceded the hematological relapse by approximately 4 months (mean time 129 days; range 6-298). The prognostic significance of WT1 expression was analyzed in 30 patients with AML. WT1 expression higher than 20 WT1 copies /10(4)ABL copies after induction and consolidation chemotherapy was associated with shorter OS. WT1 expression analysis could be a useful tool for MRD monitoring in acute leukemia.
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[Angiogenesis in different clinical phases of chronic myeloid leukemia].
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 results from an imbalance between pro- and antiangiogenic regulatory mechanisms. The investigation was focus... [more] 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 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.
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2.43Impact points
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1.17Impact points
The gain-of-function JAK2 V617F mutation shifts the phenotype of essential thrombocythemia and chronic idiopathic myelofibrosis to more "erythremic" and less "thrombocythemic": a molecular, histologic, and clinical study.
International journal of hematology. 09/2007; 86(2):130-6.
We investigated the prevalence of the JAK2 V617F gain-of-function mutation in patients with Philadelphia chromosome-negative chronic myeloproliferative disorders (Ph- MPD) and explored the links between JAK2 mutational status and the clinicopathologic picture of essential thrombocythemia (ET), chron... [more] We investigated the prevalence of the JAK2 V617F gain-of-function mutation in patients with Philadelphia chromosome-negative chronic myeloproliferative disorders (Ph- MPD) and explored the links between JAK2 mutational status and the clinicopathologic picture of essential thrombocythemia (ET), chronic idiopathic myelofibrosis (CIMF), and polycythemia vera (PV). Allele-specific polymerase chain reaction results for 59 ET, 18 CIMF, and 9 PV cases were compared with values for clinical variables at presentation and last follow-up and with the diagnostic trephine bone marrow biopsy pictures. JAK2 V617F was found in 38 (64%) of ET cases, 7 (39%) of CIMF cases, and 9 (100%) of PV cases. The ET patients with the mutant JAK2 showed significantly higher (although not overtly polycythemic) red blood cell parameter values, lower platelet counts, and higher white blood cell counts. Similar trends were found in CIMF. Megakaryocyte clustering was much less pronounced in the CIMF cases with mutant JAK2, with an analogous trend occurring in the ET cases. Bone marrow cellularity values and the numbers of CD34+ and CD117+ blasts in the ET and CIMF groups did not differ. Fibrosis was slightly less marked in the ET cases with mutant JAK2. The mutation did not significantly influence the clinical course during the follow-up in either disease in the short term (median follow-up, 22 months). The JAK2 V617F mutation is prevalent in all Ph- MPD and may skew their presenting phenotype, including bone marrow histology, toward a more "erythremic" and less "thrombocythemic" phenotype.
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2.40Impact points
Clonal lymphocytic populations in Philadelphia-negative chronic myeloproliferative disorders: is the T-cell clonality of 'undetermined' significance (TCUS) linked to a worse clinical outcome?
Leukemia & lymphoma. 12/2006; 47(11):2351-8.
This study examined the clonality of B- and T-cells by PCR in 83 patients with Philadelphia-negative myeloproliferative disorders (Ph-MPD), to investigate its clinical and morphological correlates. Clonal lymphocytic populations were found in 23% of patients (T: n = 20, B: n = 3), with no frequency ... [more] This study examined the clonality of B- and T-cells by PCR in 83 patients with Philadelphia-negative myeloproliferative disorders (Ph-MPD), to investigate its clinical and morphological correlates. Clonal lymphocytic populations were found in 23% of patients (T: n = 20, B: n = 3), with no frequency differences between ET, CIMF and PV. At the presentation, patients with clonal bands were older (58.1+/-13.8 vs 47.5+/-14.6, p = 0.0039), but did not differ in other clinical parameters. After the median follow-up of 21 months they were less likely to be asymptomatic (11.8% vs 41.1%, p = 0.029). The T-cell clonality was the strongest predictor of the symptomatic last follow-up by discriminant function analysis, surpassing the patient's age. This surprising negative prognostic impact of lymphocyte clonality in Ph-MPD may result from this phenomenon to be a better measure of the 'hematopoietic biologic age' than the metrical age itself.
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4.66Impact points
The effect of beta-carotene and its derivatives on cytotoxicity, differentiation, proliferative potential and apoptosis on the three human acute leukemia cell lines: U-937, HL-60 and TF-1.
Biochimica et biophysica acta. 06/2005; 1740(2):206-14.
The influence of beta-carotene (BC) and its derivatives on differentiation, proliferation and apoptosis in three human acute leukemia cell lines was studied. We investigated: (i) the cellular uptake of BC, (ii) the cytotoxicity, (iii) the effect on cell cycle progression and/or apoptosis. The dose- ... [more] The influence of beta-carotene (BC) and its derivatives on differentiation, proliferation and apoptosis in three human acute leukemia cell lines was studied. We investigated: (i) the cellular uptake of BC, (ii) the cytotoxicity, (iii) the effect on cell cycle progression and/or apoptosis. The dose- and time-dependent pattern of cellular BC uptake in all studied cell lines was seen. We did not observe any cytotoxic effect of BC and ATRA in the chosen concentrations. There was only limited effect of BC on gene expression. The microarrray analysis of U-937 cell line exposed to BC for 72 h showed an increased expression of BAX gene. This finding was confirmed by real-time Q-PCR analysis, and supported by a flow cytometry apoptosis tests. We did not observe any influence of studied components on cellular proliferation. The induction of differentiation after incubation with ATRA in HL-60 cells was noted. The induction of cellular apoptosis by BC was seen in all studied cell lines. We demonstrated that BC used in the concentrations achievable in vivo does not affect the proliferation and differentiation process of the studied leukemic cell lines, but can influence and enhance the apoptosis by modulating the expression of the regulatory genes.
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1.97Impact points
The microarray expression analysis identifies BAX as a mediator of beta-carotene effects on apoptosis.
Nutrition and cancer. 02/2005; 51(2):226-35.
Beta-carotene is a ubiquitous compound rich in foods. However, there are conflicting reports regarding its role in carcinogenesis. We performed a microarray expression analysis in normal [human umbilical vein endothelial cells (HUVECs)] and neoplastic (melanoma A375 and myelomonocytic leukemia U937)... [more] Beta-carotene is a ubiquitous compound rich in foods. However, there are conflicting reports regarding its role in carcinogenesis. We performed a microarray expression analysis in normal [human umbilical vein endothelial cells (HUVECs)] and neoplastic (melanoma A375 and myelomonocytic leukemia U937) actively proliferating cells and found evidence that beta-carotene stimulated vital cellular functions in the former and suppressed them in the latter. These differential effects correlated with the expression of the proapoptotic BCL2-associated X protein (BAX), which was downregulated in HUVECs and upregulated in the two neoplastic cell lines. The quantitative expression analysis using real-time polymerase chain reaction largely confirmed the inhibition of B-cell CLL/lymphoma 2 (BCL2) pathway-mediated apoptosis in HUVECs and its activation in melanoma and leukemic cells. The assays for apoptosis, detecting DNA breaks and caspase activation, showed consistent proapoptotic and antiapoptotic effects in U937 and HUVEC lines, respectively. However, beta-carotene-induced expression changes of BAX and other BCL2 pathway genes did not lead to the predicted induction of apoptosis in the A375 cells.
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2.36Impact points
ABL-kinase domain point mutation as a cause of imatinib (STI571) resistance in CML patient who progress to myeloid blast crisis.
Leukemia research. 01/2004; 27(12):1163-6.
Imatinib mesylate (STI571) is a major therapeutic advance for the management of chronic myeloid leukaemia (CML), however, a proportion of patients are refractory to it, particularly those in more advanced phases of CML. Different mechanisms of resistance to imatinib are suggested, including point mu... [more] Imatinib mesylate (STI571) is a major therapeutic advance for the management of chronic myeloid leukaemia (CML), however, a proportion of patients are refractory to it, particularly those in more advanced phases of CML. Different mechanisms of resistance to imatinib are suggested, including point mutations within ABL-kinase domains. A point mutation leading to substitution at the ATP binding site of ABL-kinase and insensitivity to imatinib was detected in our patient treated with imatinib, who progressed to blast crisis. Additionally, clonal evolution could lead to BCR-ABL-independent proliferation. Early detection of ABL-kinase mutation could predict the progression of CML treated with imatinib.
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6.42Impact points
Idiopathic myelofibrosis with fatty bone marrow: an issue of sampling? A propos an unusual case.
Haematologica. 04/2003; 88(3):ELT05.
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[Harvesting bone marrow from the posterior superior iliac crest for transplantation]
Przegla̧d lekarski. 02/1999; 56 Suppl 1:40-3.
The purpose of bone marrow cells harvesting is to isolate haemopoietic stem cell for the transplantation, by means of multiple punctures from the posterior iliac crest under general anaesthesia. This method is the alternative procedure for collecting circulating peripheral blood progenitor cells per... [more] The purpose of bone marrow cells harvesting is to isolate haemopoietic stem cell for the transplantation, by means of multiple punctures from the posterior iliac crest under general anaesthesia. This method is the alternative procedure for collecting circulating peripheral blood progenitor cells performed with continuous-flow cell separators. The aim of the both procedures is the collection of progenitor cells for transplantation in the number enabling reconstitution of marrow function after myeloablative therapy. The bone marrow cell harvesting is a safe measure: the infrequent complication related to general anaesthesia may occur and the simultaneous or subsequent blood transfusion is usually required.
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[Molecular basis of chronic myelogenous leukemia and significance of diagnostic methods based on BCR-ABL gene amplification]
Przegla̧d lekarski. 02/1999; 56 Suppl 1:57-61.
Chronic myelogenous leukemia is characterized by an abnormal 22nd chromosome known as a Philadelphia chromosome, which can be detected in 95% of patients with CML. Molecular equivalent of this aberration is a BCR-ABL translocation resulting in chimeric gene formation. A BCR-ABL chimeric gene plays a... [more] Chronic myelogenous leukemia is characterized by an abnormal 22nd chromosome known as a Philadelphia chromosome, which can be detected in 95% of patients with CML. Molecular equivalent of this aberration is a BCR-ABL translocation resulting in chimeric gene formation. A BCR-ABL chimeric gene plays a key role in the hematopoietic cells proliferation regulation. RT-PCR can be used in diagnosis of CML, to detect chimeric BCR-ABL gene, and to reveal the type of translocation what could have prognostic importance, and in monitoring of minimal residual disease, confirming the eradication of pathological cells clone after treatment and identifying the group of patients with best prognosis and best overall survival. RT-PCR in monitoring of minimal residual disease after allo- or autologous hemopoietic cells transplantation can early reveal relapse of the disease. Detection of molecular relapse is an important prognostic factor and may implicate induction of treatment which should prevent haematological relapse of the disease.
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[Autologous hemopoietic stem cell transplantation in treatment of chronic myelogenous leukemia]
Przegla̧d lekarski. 02/1999; 56 Suppl 1:62-6.
Chronic myelogenous leukemia in more than 90% of patients is associated with the abnormal Philadelphia chromosome, which results in aberrant BCR-ABL chimeric gene expression. The mean overall survival on standard chemotherapy (which is not curative) ranges between 54-72 months. Selected patients wit... [more] Chronic myelogenous leukemia in more than 90% of patients is associated with the abnormal Philadelphia chromosome, which results in aberrant BCR-ABL chimeric gene expression. The mean overall survival on standard chemotherapy (which is not curative) ranges between 54-72 months. Selected patients with CML can be cured by allogeneic hemopoietic stem cell transplantation. Only 30% of patients has an optimal HLA-identical sibling donor. It is possible to find well-matched unrelated donor for another 20-30% of patients, however matched-unrelated donor transplantation is still associated with relative high risk of complications and cannot be used in elderly patients. Interferon alpha treatment in monotherapy or in combination with ARA-C can induce a cytogenetical and molecular remission in selected group of patients, which benefits with significantly prolonged survival. Nevertheless the cost of this treatment is high and long period of therapy is required to assess its efficacy. In patients lacking matched related or unrelated donors for allogeneic transplantation, autologous stem cell transplantation could be the alternative method of treatment. Discussed in the paper method of mobilization and transplantation of Philadelphia-negative peripheral-blood progenitor cells collected during early phase of bone marrow regeneration after "mobilizing" chemotherapy (mini-ICE) enables to achieve a complete or major cytogenetical response in about 77% of patients. There is only minimal morbidity and no transplant-related mortality. This procedure and the post-transplant immunotherapy (IFN alpha, interleukin-2) can considerably suppress the pathological clone and significantly prolong the overall survival in CML patients not eligible for allogeneic transplantation.
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[The effect of magnesium on blood coagulation--state of the art literature review from 1959 to 1995]
Przegla̧d lekarski. 02/1997; 54(2):122-5.
The effect of magnesium on coagulation system is still an interesting subject for investigations. Shionoya in his publication (1927) reported for the first time possible inhibitory effect of magnesium on coagulation system. Since then, a large number of studies were undertaken to explain the mechani... [more] The effect of magnesium on coagulation system is still an interesting subject for investigations. Shionoya in his publication (1927) reported for the first time possible inhibitory effect of magnesium on coagulation system. Since then, a large number of studies were undertaken to explain the mechanisms of influence of Mg++ on plasma coagulation, platelet function and fibrinolysis. In recent decades, the effect of magnesium on coagulation has led to controversy in a wide range of scientific publications. At present, series of experiments are undertaken in laboratories using modern methodology to evaluate the possible effect of magnesium on coagulation. The results of Anders's and Frisch's study reported here support the theory of the authors, who found no change in coagulation in the presence of physiological concentration of magnesium in blood serum. The influence on the final results, often contradictory, could have: different type of study (in vitro or in vivo), the object of the study (human being, animal), concentrations of magnesium (in most of cases non-physiologic and toxic) and out of date methodology. In majority of reported here studies there were no control groups, and clinical trials were not a double blind studies.
Following (6)
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Krzysztof Okoń
Uniwersytet Jagielloński -
Christoph Moehle
Universität Regensburg -
Wojciech Placha
Collegium Medicum of the Jagiellonian University -
Joanna Dulińska-Litewka
Uniwersytet Jagielloński -
Bartosz Wasag
Medical University of Gdansk
Topics (2)
