Helena Podgornik - Academia.edu (original) (raw)

Papers by Helena Podgornik

Research paper thumbnail of Cytogenetic complexity in chronic lymphocytic leukemia: definitions, associations, and clinical impact

Blood, 2019

Recent evidence suggests that complex karyotype (CK) defined by the presence of ≥3 chromosomal ab... more Recent evidence suggests that complex karyotype (CK) defined by the presence of ≥3 chromosomal aberrations (structural and/or numerical) identified by using chromosome-banding analysis (CBA) may be relevant for treatment decision-making in chronic lymphocytic leukemia (CLL). However, many challenges toward the routine clinical application of CBA remain. In a retrospective study of 5290 patients with available CBA data, we explored both clinicobiological associations and the clinical impact of CK in CLL. We found that patients with ≥5 abnormalities, defined as high-CK, exhibit uniformly dismal clinical outcomes, independently of clinical stage, TP53 aberrations (deletion of chromosome 17p and/or TP53 mutations [TP53abs]), and the expression of somatically hypermutated (M-CLL) or unmutated immunoglobulin heavy variable genes. Thus, they contrasted with CK cases with 3 or 4 aberrations (low-CK and intermediate-CK, respectively) who followed aggressive disease courses only in the presen...

Research paper thumbnail of Chronic Lymphocytic Leukemia with Divergent Richter’s Transformation into a Clonally Related Classical Hodgkin’s and Plasmablastic Lymphoma: A Case Report

Case Reports in Oncology

Chronic lymphocytic leukemia (CLL) typically pursues a prolonged course. Its transformation into ... more Chronic lymphocytic leukemia (CLL) typically pursues a prolonged course. Its transformation into a more aggressive lymphoma occurs in 2–8% of all patients. Most commonly, diffuse large B-cell lymphoma develops. Transformation into a classical Hodgkin’s lymphoma (cHL) occurs in <1%. Plasmablastic transformation has been only rarely reported. Cases of synchronous divergent transformation of CLL into a composite lymphoma are exceedingly rare. We describe the unique occurrence of the transformation of a long-standing CLL into a synchronous clonally related cHL as well as plasmablastic lymphoma (PBL) in an 85-year-old female patient. After 10 years of asymptomatic CLL, our patient was treated with a rituximab-chlorambucil scheme in combination with pegfilgrastim for recurrent infections and the development of B symptoms. Five cycles (of six planned) were administrated with no adverse effects. After the fifth cycle, lymphadenopathy with pronounced B symptoms appeared. Histology showed ...

Research paper thumbnail of Transformation of Indigo carmine by Phanerochaete chrysosporium ligninolytic enzymes

Enzyme and microbial technology, 2001

The reaction between P. chrysosporium extracellular ligninolytic peroxidases and the dye Indigo c... more The reaction between P. chrysosporium extracellular ligninolytic peroxidases and the dye Indigo carmine was studied. This dye can be successfully decolorized by both manganese (MnP) and lignin (LiP) peroxidases. By using a proper culture medium composition, a growth medium exhibiting high MnP or high LiP activity was obtained. Additionally, some peroxidase isoenzymes were isolated. Although the dye was successfully decolorised by both groups of extracellular peroxidases, the reaction by MnP was faster. Besides a yellow final product, the decolorization of Indigo carmine by MnP resulted in a red product formation that was not observed at the decolorization by LiP. The final concentration of the red product can be influenced by the pH value of the reaction mixture as well as by the initial dye concentration. The maximum formation of the red product was achieved at pH 5 with 60 mg/liter of the Indigo carmine in the reaction mixture. The red product was isolated and partially characterized using UV-VIS and 1 H NMR spectroscopy, and TLC.

Research paper thumbnail of Decolorization rate of dyes using lignin peroxidases of Phanerochaete chrysosporium

Chemosphere, 1999

... DECOLORIZATION RATE OF DYES USING LIGNIN PEROXIDASES OF PHANEROCHAETE CHRYSOSPORIUM Helena Po... more ... DECOLORIZATION RATE OF DYES USING LIGNIN PEROXIDASES OF PHANEROCHAETE CHRYSOSPORIUM Helena Podgomik,* Irena Grgid, Anton Perdih Faculty ... Knapp JS, PS Newby, LP Reece, Decolorization of dyes by woodrotting basidiomycete fungi, Enzyme Microb. ...

Research paper thumbnail of Determination of imatinib intracellular uptake in leukocytes as a prognostic factor in cML therapy

Slovenian Medical Journal, Jan 12, 2012

Izhodišča: Imatinib je prvo usmerjeno zdravilo pri zdravljenju kronične mieloične levkemije (KML)... more Izhodišča: Imatinib je prvo usmerjeno zdravilo pri zdravljenju kronične mieloične levkemije (KML). Odziv bolnikov na zdravljenje z imatinibom je odvisen tudi od vstopa učinkovine v tarčno celico z organskim kationskim prenašalcem 1 (OCT1). Na osnovi privzema radioaktivno označenega imatiniba v mononuklearne (MNC) celice bolnikov pred začetkom zdravljenja je že bila dokazana povezava med aktivnostjo OCT1 prenašalcev in uspešnostjo zdravljenja. Domneva se, da bi določanje aktivnosti OCT1 pri bolnikih s KML lahko prispevalo k napovedi uspešnosti zdravljenja z imatinibom.

Research paper thumbnail of Separation and isolation of peroxidase isoenzymes from the growth medium of P. chrysosporium using monolithic columns

American biotechnology laboratory

Research paper thumbnail of Analysis of Fungal Pellets by UV-Visible Spectrum Diffuse Reflectance Spectroscopy

Applied and Environmental Microbiology

The application of the UV-visible spectrum diffuse reflectance spectroscopy for the determination... more The application of the UV-visible spectrum diffuse reflectance spectroscopy for the determination of intracellular pH in vivo, for determination of cytochrome content, and for the noninvasive in vivo detection of the redox state of fungal mitochondrial cytochromes in filamentous fungi is introduced. The time course of the intracellular pH values, mitochondrial cytochromes, and CO-binding pigments content and the correlations between the actual redox state of cytochrome aa3 and saturation of growth medium with oxygen in pellets of the basidiomycete Phanerochaete chrysosporium were determined. As the test microorganism, the yeast Saccharomyces cerevisiae was used. UV-visible spectrum diffuse reflectance spectroscopy proved to be a promising method for the quick and simple analysis of light-impermeable biological structures for which the classical transmittance spectrophotometric methods are difficult to implement.

Research paper thumbnail of Ligninolytic enzyme production in cultures of Irpex lacteus and Phanerochaete chrysosporium and their implication in dye decolorization

Research paper thumbnail of ATO Metabolites in APL an MM Patients Treated According to APL and MAC/DAC Schemes

Research paper thumbnail of Improvements in the determination of manganese peroxidase activity

ABSTRACT The existing method of determining the activity of manganese peroxidase (MnP), produced ... more ABSTRACT The existing method of determining the activity of manganese peroxidase (MnP), produced by Phanerochaete chrysosporium, was improved. 2,6-Dimethoxyphenol at 80 mM was used as a substrate and, after the decolorization of the reaction mixture, H2O2 was added and the initial reaction rate was used to determine MnP activity.

Research paper thumbnail of Arsenic metabolism in multiple myeloma and astrocytoma cells

Biological Trace Element Research, 2007

Arsenic trioxide (As2O3, Trisenox®) is used to treat patients with refractory or relapsed acute p... more Arsenic trioxide (As2O3, Trisenox®) is used to treat patients with refractory or relapsed acute promyelocytic leukemia (APL). Its ability to induce apoptosis in various malignant cell lines has made it a potential treatment agent for other malignancies and many clinical trials are currently in progress to evaluate its clinical usefulness for multiple myeloma and glioblastoma cancer. In the present study,

Research paper thumbnail of CITOGENETIČNE IN MOLEKULARNOGENETIČNE PREISKAVE PRI UGOTAVLJANJU KRONIČNE MIELOIČNE LEVKEMIJE IN SPREMLJANJU ZDRAVLJENJA THE ROLE OF CYTOGENETICS AND MOLECULAR GENETICS IN DIAGNOSIS OF CHRONIC MYELOID LEUKEMIA AND MONITORING OF TREATMENT RESPONSE

Background. Chronic myeloid leukemia serves as a model for the disease where the knowledge as wel... more Background. Chronic myeloid leukemia serves as a model for the disease where the knowledge as well as the development of different new methods from molecular bio- logy were successfully introduced into the clinical practice. Methods. Standard cytogenetic analysis was primarily used for detecting the translocation between chromosomes 9 and 22: t(9;22) while fluorescence in situ hybridization (FISH) and real time

Research paper thumbnail of Arsenic metabolism in multiple myeloma and astrocytoma cells

Biological Trace Element Research, 2007

Arsenic trioxide (As2O3, Trisenox) is used to treat patients with refractory or relapsed acute pr... more Arsenic trioxide (As2O3, Trisenox) is used to treat patients with refractory or relapsed acute promyelocytic leukemia (APL). Its ability to induce apoptosis in various malignant cell lines has made it a potential treatment agent for other malignancies and many clinical trials are currently in progress to evaluate its clinical usefulness for multiple myeloma and glioblastoma cancer. In the present study, we investigated the metabolism of As2O3 regarding its cellular biotransformation and interaction with metallothionein (MT) as a possible protective responses of cells to arsenic-induced cytotoxicity. The study was performed on two types of cell treated with As2O3: (1) human astrocytoma (glioblastoma) cell line U87MG treated with 0.6 microM arsenic for 0, 3, 12, 24, and 48 h or 12 microM arsenic for 3, 6, 12, 24, and 48 h and (2) bone marrow cells (BM) from two patients with multiple myeloma (MM) treated with 7 microM arsenic for 0, 43, and 67 h. Cotreatment with vitamin C (1 mg/mL) was tested in longer exposure of MM BM cells. Traces of methylation products (mainly monomethylarsenic acid) were detected in cell lysates of both cell types and in pellets of U87 MG cells, although we found problems with column-sample interactions in cases where methanol pretreatment of the sample was not used. Pentavalent inorganic arsenic (AsV) was identified in both cell types, and up to 80% of total As in MM bone marrow cell lysates was present as AsV. Such an occurrence (generation) of pentavalent arsenic after As2O3 treatment demonstrates the presence of biological oxidation of trivalent arsenic, which could represent an additional protective mechanism of the cell. Vitamin C decreased As cell content and increased the percentage of pentavalent inorganic arsenic (in the growth medium and cells). The presence of metallothionein (MT) and its response to arsenic treatment was checked in all U87 MG cells, in the control, and in one exposed sample of MM BM cells. During 48 h exposure to 0.6 or 12 muM arsenic MTI/II levels increased in U87 MG cells, but with variable Zn levels, increased Cu levels, and As binding observed in traces only. Involvement of the MT-III isoform was negligible. In contrast, 43 h exposure to 7 microMarsenic did not increase MT content in multiple myeloma cells, and the levels even decreased with respect to the control. To evaluate the importance of the observed processes, MTs in U87 and AsIII-AsV conversion in MM BM cells, which could represent a resistance response of cancer cells treated by As2O3, longer-term observation with different arsenic concentrations should be performed.

Research paper thumbnail of Development of treatment and clinical results in childhood acute myeloid leukemia in Poland

memo - Magazine of European Medical Oncology, 2012

Background Since the early 1990s, three consecutive pediatric acute myeloid leukemia (AML) trials... more Background Since the early 1990s, three consecutive pediatric acute myeloid leukemia (AML) trials have been performed in Austria (AML-Berlin-Frankfurt-Münster (BFM) 93, AML-BFM 98, and AML-BFM 2004) in close cooperation with the international BFM study center.

Research paper thumbnail of Impact of pellet size on growth and lignin peroxidase activity of Phanerochaete chrysosporium

World Journal of Microbiology and Biotechnology, 2006

ABSTRACT We investigated the influence of pellet size on the growth and lignin peroxidase (LiP) p... more ABSTRACT We investigated the influence of pellet size on the growth and lignin peroxidase (LiP) productivity of Phanerochaete chrysosporium. Different pellet sizes were obtained by varying the vessel diameter under constant shaking conditions. Under these varying conditions the pellet size was in the range of 2–18mm, while the number of pellets in a single vessel varied from around 1,200 in the Erlenmeyer flask to around 6 in the narrowest vessel. A correlation between the final pellet size and the shear rate was obtained, demonstrating that the pellet size is mainly affected by hydrodynamics. The growth of large pellets was described by a cubic growth model. Despite different pellet sizes, LiP activity appeared in all vessels, but the onset of LiP activity showed a delay based upon the pellet size, while maximal LiP activities varied by only 15%, being around 850U/l.

Research paper thumbnail of Immobilisation and characteristics of glucose oxidase immobilised on convective interaction media (CIM) disks

Progress in …, 1998

... Josi6, Anal. Chem., 68 (1996) 3483. 4. Dj. Josid, H. Schwinn, A. ~trancar, A. Podgornik, M. B... more ... Josi6, Anal. Chem., 68 (1996) 3483. 4. Dj. Josid, H. Schwinn, A. ~trancar, A. Podgornik, M. Barut, YP. Lira and M. Vodopivec, J. Chromatogr. ... 2. A. Štrancar, Ph.D. Thesis, BIA doo, Ljubljana (1997). 3. A. Štrancar, P. Koselj, H. Schwinn and Dj. Josić. Anal. ...

Research paper thumbnail of Laccase production by Phanerochaete chrysosporium - an artefact caused by Mn(III)?

Letters in Applied Microbiology, 2001

Aims: The possibility of laccase production by Phanerochaete chrysosporium was studied. Methods a... more Aims: The possibility of laccase production by Phanerochaete chrysosporium was studied. Methods and Results: A relatively high initial Mn(II) concentration (1±4 mM) in the growth medium leads to the development of reddish-brown coloration and intensive oxidation of 2.2¢-azino-bis(3-etilbenz-tiazolin-6-sulfonate) (ABTS). The peak of ABTS oxidation was obtained approximately 1 day after the peak of MnP activity. Conclusions: ABTS oxidation was not caused by manganese peroxidase (MnP) nor by laccase but was the consequence of the action of Mn(III) which was stabilised in the growth medium. Decomposition of the complex took place after the biomass was removed from the growth medium and especially after the aeration of the culture was interrupted. Signi®cance and Impact of the Study: Mn(III) seems to be the cause of false positive laccase reactions. More reliable data on MnP activity can be obtained if the complex is decomposed by the fungus before MnP activity is measured in the medium.

Research paper thumbnail of Transfer of gradient chromatographic methods for protein separation to Convective Interaction Media monolithic columns

Journal of Chromatography A, 2003

Research paper thumbnail of Concurrent rearrangements of BCL2 , BCL3 , and BCL11A genes in atypical chronic lymphocytic leukemia

Hematology, 2014

The most frequent chromosomal aberrations with the well established prognostic meaning in chronic... more The most frequent chromosomal aberrations with the well established prognostic meaning in chronic lymphocytic leukemia (CLL) are +12, del(11q), del(13q), and del(17p). Less common translocations lead to deregulation of genes primarily due to juxtaposition with IGH gene. We present a case of CLL patient with atypical morphology and an aggressive course of disease. In spite of aggressive treatment including allogeneic hematopoietic stem cell transplantation disease progressed into a rare cutaneous Richter&amp;amp;amp;amp;amp;amp;amp;amp;#39;s syndrome. Trisomy 12 was found as a sole chromosomal change at initial cytogenetic analysis of lymphoma cells. At progression, besides trisomy 12 three concomitant balanced translocations t(2;14)(p13;q32), t(14;19)(q32;q13), and t(18;22)(q21;q11) were found. The same karyotype was confirmed in cells aspirated from skin infiltrates at Richter transformation. Atypical cytological features, trisomy 12, and a progressive course of disease observed in our case are typical for CLL with each of particular Ig translocations that were concomitantly found in CLL for the first time. Similar to &amp;amp;amp;amp;amp;amp;amp;amp;quot;double hit&amp;amp;amp;amp;amp;amp;amp;amp;quot; lymphoma concurrent rearrangements may be relevant also in CLL.

Research paper thumbnail of Selective apoptosis of multiple myeloma cells in primary samples induced by arsenic trioxide

Hematology, 2013

Currently, multiple myeloma (MM) is an incurable disease. Despite the fact that arsenic trioxide ... more Currently, multiple myeloma (MM) is an incurable disease. Despite the fact that arsenic trioxide (ATO) shows promising results in vitro, data from treatment of patients with MM are disappointing. Due to these discrepancies, we compared the efficacy and selectivity of ATO at two different concentrations in samples from MM patients. The extent of apoptosis induced by 2 and 5 µM ATO was evaluated by flow cytometry using annexin V. 34 diagnostic bone marrow samples obtained from MM patients were analysed. 5 µM ATO efficiently induced apoptosis in primary samples. Besides efficacy, also selectivity of action on MM cells in comparison to remaining haematopoietic cells was demonstrated for 5 µM ATO but not for 2 µM ATO. Our study on primary samples confirmed that ATO has a potential role in therapeutic management of MM. Further controlled studies on MM patients are needed.

Research paper thumbnail of Cytogenetic complexity in chronic lymphocytic leukemia: definitions, associations, and clinical impact

Blood, 2019

Recent evidence suggests that complex karyotype (CK) defined by the presence of ≥3 chromosomal ab... more Recent evidence suggests that complex karyotype (CK) defined by the presence of ≥3 chromosomal aberrations (structural and/or numerical) identified by using chromosome-banding analysis (CBA) may be relevant for treatment decision-making in chronic lymphocytic leukemia (CLL). However, many challenges toward the routine clinical application of CBA remain. In a retrospective study of 5290 patients with available CBA data, we explored both clinicobiological associations and the clinical impact of CK in CLL. We found that patients with ≥5 abnormalities, defined as high-CK, exhibit uniformly dismal clinical outcomes, independently of clinical stage, TP53 aberrations (deletion of chromosome 17p and/or TP53 mutations [TP53abs]), and the expression of somatically hypermutated (M-CLL) or unmutated immunoglobulin heavy variable genes. Thus, they contrasted with CK cases with 3 or 4 aberrations (low-CK and intermediate-CK, respectively) who followed aggressive disease courses only in the presen...

Research paper thumbnail of Chronic Lymphocytic Leukemia with Divergent Richter’s Transformation into a Clonally Related Classical Hodgkin’s and Plasmablastic Lymphoma: A Case Report

Case Reports in Oncology

Chronic lymphocytic leukemia (CLL) typically pursues a prolonged course. Its transformation into ... more Chronic lymphocytic leukemia (CLL) typically pursues a prolonged course. Its transformation into a more aggressive lymphoma occurs in 2–8% of all patients. Most commonly, diffuse large B-cell lymphoma develops. Transformation into a classical Hodgkin’s lymphoma (cHL) occurs in <1%. Plasmablastic transformation has been only rarely reported. Cases of synchronous divergent transformation of CLL into a composite lymphoma are exceedingly rare. We describe the unique occurrence of the transformation of a long-standing CLL into a synchronous clonally related cHL as well as plasmablastic lymphoma (PBL) in an 85-year-old female patient. After 10 years of asymptomatic CLL, our patient was treated with a rituximab-chlorambucil scheme in combination with pegfilgrastim for recurrent infections and the development of B symptoms. Five cycles (of six planned) were administrated with no adverse effects. After the fifth cycle, lymphadenopathy with pronounced B symptoms appeared. Histology showed ...

Research paper thumbnail of Transformation of Indigo carmine by Phanerochaete chrysosporium ligninolytic enzymes

Enzyme and microbial technology, 2001

The reaction between P. chrysosporium extracellular ligninolytic peroxidases and the dye Indigo c... more The reaction between P. chrysosporium extracellular ligninolytic peroxidases and the dye Indigo carmine was studied. This dye can be successfully decolorized by both manganese (MnP) and lignin (LiP) peroxidases. By using a proper culture medium composition, a growth medium exhibiting high MnP or high LiP activity was obtained. Additionally, some peroxidase isoenzymes were isolated. Although the dye was successfully decolorised by both groups of extracellular peroxidases, the reaction by MnP was faster. Besides a yellow final product, the decolorization of Indigo carmine by MnP resulted in a red product formation that was not observed at the decolorization by LiP. The final concentration of the red product can be influenced by the pH value of the reaction mixture as well as by the initial dye concentration. The maximum formation of the red product was achieved at pH 5 with 60 mg/liter of the Indigo carmine in the reaction mixture. The red product was isolated and partially characterized using UV-VIS and 1 H NMR spectroscopy, and TLC.

Research paper thumbnail of Decolorization rate of dyes using lignin peroxidases of Phanerochaete chrysosporium

Chemosphere, 1999

... DECOLORIZATION RATE OF DYES USING LIGNIN PEROXIDASES OF PHANEROCHAETE CHRYSOSPORIUM Helena Po... more ... DECOLORIZATION RATE OF DYES USING LIGNIN PEROXIDASES OF PHANEROCHAETE CHRYSOSPORIUM Helena Podgomik,* Irena Grgid, Anton Perdih Faculty ... Knapp JS, PS Newby, LP Reece, Decolorization of dyes by woodrotting basidiomycete fungi, Enzyme Microb. ...

Research paper thumbnail of Determination of imatinib intracellular uptake in leukocytes as a prognostic factor in cML therapy

Slovenian Medical Journal, Jan 12, 2012

Izhodišča: Imatinib je prvo usmerjeno zdravilo pri zdravljenju kronične mieloične levkemije (KML)... more Izhodišča: Imatinib je prvo usmerjeno zdravilo pri zdravljenju kronične mieloične levkemije (KML). Odziv bolnikov na zdravljenje z imatinibom je odvisen tudi od vstopa učinkovine v tarčno celico z organskim kationskim prenašalcem 1 (OCT1). Na osnovi privzema radioaktivno označenega imatiniba v mononuklearne (MNC) celice bolnikov pred začetkom zdravljenja je že bila dokazana povezava med aktivnostjo OCT1 prenašalcev in uspešnostjo zdravljenja. Domneva se, da bi določanje aktivnosti OCT1 pri bolnikih s KML lahko prispevalo k napovedi uspešnosti zdravljenja z imatinibom.

Research paper thumbnail of Separation and isolation of peroxidase isoenzymes from the growth medium of P. chrysosporium using monolithic columns

American biotechnology laboratory

Research paper thumbnail of Analysis of Fungal Pellets by UV-Visible Spectrum Diffuse Reflectance Spectroscopy

Applied and Environmental Microbiology

The application of the UV-visible spectrum diffuse reflectance spectroscopy for the determination... more The application of the UV-visible spectrum diffuse reflectance spectroscopy for the determination of intracellular pH in vivo, for determination of cytochrome content, and for the noninvasive in vivo detection of the redox state of fungal mitochondrial cytochromes in filamentous fungi is introduced. The time course of the intracellular pH values, mitochondrial cytochromes, and CO-binding pigments content and the correlations between the actual redox state of cytochrome aa3 and saturation of growth medium with oxygen in pellets of the basidiomycete Phanerochaete chrysosporium were determined. As the test microorganism, the yeast Saccharomyces cerevisiae was used. UV-visible spectrum diffuse reflectance spectroscopy proved to be a promising method for the quick and simple analysis of light-impermeable biological structures for which the classical transmittance spectrophotometric methods are difficult to implement.

Research paper thumbnail of Ligninolytic enzyme production in cultures of Irpex lacteus and Phanerochaete chrysosporium and their implication in dye decolorization

Research paper thumbnail of ATO Metabolites in APL an MM Patients Treated According to APL and MAC/DAC Schemes

Research paper thumbnail of Improvements in the determination of manganese peroxidase activity

ABSTRACT The existing method of determining the activity of manganese peroxidase (MnP), produced ... more ABSTRACT The existing method of determining the activity of manganese peroxidase (MnP), produced by Phanerochaete chrysosporium, was improved. 2,6-Dimethoxyphenol at 80 mM was used as a substrate and, after the decolorization of the reaction mixture, H2O2 was added and the initial reaction rate was used to determine MnP activity.

Research paper thumbnail of Arsenic metabolism in multiple myeloma and astrocytoma cells

Biological Trace Element Research, 2007

Arsenic trioxide (As2O3, Trisenox®) is used to treat patients with refractory or relapsed acute p... more Arsenic trioxide (As2O3, Trisenox®) is used to treat patients with refractory or relapsed acute promyelocytic leukemia (APL). Its ability to induce apoptosis in various malignant cell lines has made it a potential treatment agent for other malignancies and many clinical trials are currently in progress to evaluate its clinical usefulness for multiple myeloma and glioblastoma cancer. In the present study,

Research paper thumbnail of CITOGENETIČNE IN MOLEKULARNOGENETIČNE PREISKAVE PRI UGOTAVLJANJU KRONIČNE MIELOIČNE LEVKEMIJE IN SPREMLJANJU ZDRAVLJENJA THE ROLE OF CYTOGENETICS AND MOLECULAR GENETICS IN DIAGNOSIS OF CHRONIC MYELOID LEUKEMIA AND MONITORING OF TREATMENT RESPONSE

Background. Chronic myeloid leukemia serves as a model for the disease where the knowledge as wel... more Background. Chronic myeloid leukemia serves as a model for the disease where the knowledge as well as the development of different new methods from molecular bio- logy were successfully introduced into the clinical practice. Methods. Standard cytogenetic analysis was primarily used for detecting the translocation between chromosomes 9 and 22: t(9;22) while fluorescence in situ hybridization (FISH) and real time

Research paper thumbnail of Arsenic metabolism in multiple myeloma and astrocytoma cells

Biological Trace Element Research, 2007

Arsenic trioxide (As2O3, Trisenox) is used to treat patients with refractory or relapsed acute pr... more Arsenic trioxide (As2O3, Trisenox) is used to treat patients with refractory or relapsed acute promyelocytic leukemia (APL). Its ability to induce apoptosis in various malignant cell lines has made it a potential treatment agent for other malignancies and many clinical trials are currently in progress to evaluate its clinical usefulness for multiple myeloma and glioblastoma cancer. In the present study, we investigated the metabolism of As2O3 regarding its cellular biotransformation and interaction with metallothionein (MT) as a possible protective responses of cells to arsenic-induced cytotoxicity. The study was performed on two types of cell treated with As2O3: (1) human astrocytoma (glioblastoma) cell line U87MG treated with 0.6 microM arsenic for 0, 3, 12, 24, and 48 h or 12 microM arsenic for 3, 6, 12, 24, and 48 h and (2) bone marrow cells (BM) from two patients with multiple myeloma (MM) treated with 7 microM arsenic for 0, 43, and 67 h. Cotreatment with vitamin C (1 mg/mL) was tested in longer exposure of MM BM cells. Traces of methylation products (mainly monomethylarsenic acid) were detected in cell lysates of both cell types and in pellets of U87 MG cells, although we found problems with column-sample interactions in cases where methanol pretreatment of the sample was not used. Pentavalent inorganic arsenic (AsV) was identified in both cell types, and up to 80% of total As in MM bone marrow cell lysates was present as AsV. Such an occurrence (generation) of pentavalent arsenic after As2O3 treatment demonstrates the presence of biological oxidation of trivalent arsenic, which could represent an additional protective mechanism of the cell. Vitamin C decreased As cell content and increased the percentage of pentavalent inorganic arsenic (in the growth medium and cells). The presence of metallothionein (MT) and its response to arsenic treatment was checked in all U87 MG cells, in the control, and in one exposed sample of MM BM cells. During 48 h exposure to 0.6 or 12 muM arsenic MTI/II levels increased in U87 MG cells, but with variable Zn levels, increased Cu levels, and As binding observed in traces only. Involvement of the MT-III isoform was negligible. In contrast, 43 h exposure to 7 microMarsenic did not increase MT content in multiple myeloma cells, and the levels even decreased with respect to the control. To evaluate the importance of the observed processes, MTs in U87 and AsIII-AsV conversion in MM BM cells, which could represent a resistance response of cancer cells treated by As2O3, longer-term observation with different arsenic concentrations should be performed.

Research paper thumbnail of Development of treatment and clinical results in childhood acute myeloid leukemia in Poland

memo - Magazine of European Medical Oncology, 2012

Background Since the early 1990s, three consecutive pediatric acute myeloid leukemia (AML) trials... more Background Since the early 1990s, three consecutive pediatric acute myeloid leukemia (AML) trials have been performed in Austria (AML-Berlin-Frankfurt-Münster (BFM) 93, AML-BFM 98, and AML-BFM 2004) in close cooperation with the international BFM study center.

Research paper thumbnail of Impact of pellet size on growth and lignin peroxidase activity of Phanerochaete chrysosporium

World Journal of Microbiology and Biotechnology, 2006

ABSTRACT We investigated the influence of pellet size on the growth and lignin peroxidase (LiP) p... more ABSTRACT We investigated the influence of pellet size on the growth and lignin peroxidase (LiP) productivity of Phanerochaete chrysosporium. Different pellet sizes were obtained by varying the vessel diameter under constant shaking conditions. Under these varying conditions the pellet size was in the range of 2–18mm, while the number of pellets in a single vessel varied from around 1,200 in the Erlenmeyer flask to around 6 in the narrowest vessel. A correlation between the final pellet size and the shear rate was obtained, demonstrating that the pellet size is mainly affected by hydrodynamics. The growth of large pellets was described by a cubic growth model. Despite different pellet sizes, LiP activity appeared in all vessels, but the onset of LiP activity showed a delay based upon the pellet size, while maximal LiP activities varied by only 15%, being around 850U/l.

Research paper thumbnail of Immobilisation and characteristics of glucose oxidase immobilised on convective interaction media (CIM) disks

Progress in …, 1998

... Josi6, Anal. Chem., 68 (1996) 3483. 4. Dj. Josid, H. Schwinn, A. ~trancar, A. Podgornik, M. B... more ... Josi6, Anal. Chem., 68 (1996) 3483. 4. Dj. Josid, H. Schwinn, A. ~trancar, A. Podgornik, M. Barut, YP. Lira and M. Vodopivec, J. Chromatogr. ... 2. A. Štrancar, Ph.D. Thesis, BIA doo, Ljubljana (1997). 3. A. Štrancar, P. Koselj, H. Schwinn and Dj. Josić. Anal. ...

Research paper thumbnail of Laccase production by Phanerochaete chrysosporium - an artefact caused by Mn(III)?

Letters in Applied Microbiology, 2001

Aims: The possibility of laccase production by Phanerochaete chrysosporium was studied. Methods a... more Aims: The possibility of laccase production by Phanerochaete chrysosporium was studied. Methods and Results: A relatively high initial Mn(II) concentration (1±4 mM) in the growth medium leads to the development of reddish-brown coloration and intensive oxidation of 2.2¢-azino-bis(3-etilbenz-tiazolin-6-sulfonate) (ABTS). The peak of ABTS oxidation was obtained approximately 1 day after the peak of MnP activity. Conclusions: ABTS oxidation was not caused by manganese peroxidase (MnP) nor by laccase but was the consequence of the action of Mn(III) which was stabilised in the growth medium. Decomposition of the complex took place after the biomass was removed from the growth medium and especially after the aeration of the culture was interrupted. Signi®cance and Impact of the Study: Mn(III) seems to be the cause of false positive laccase reactions. More reliable data on MnP activity can be obtained if the complex is decomposed by the fungus before MnP activity is measured in the medium.

Research paper thumbnail of Transfer of gradient chromatographic methods for protein separation to Convective Interaction Media monolithic columns

Journal of Chromatography A, 2003

Research paper thumbnail of Concurrent rearrangements of BCL2 , BCL3 , and BCL11A genes in atypical chronic lymphocytic leukemia

Hematology, 2014

The most frequent chromosomal aberrations with the well established prognostic meaning in chronic... more The most frequent chromosomal aberrations with the well established prognostic meaning in chronic lymphocytic leukemia (CLL) are +12, del(11q), del(13q), and del(17p). Less common translocations lead to deregulation of genes primarily due to juxtaposition with IGH gene. We present a case of CLL patient with atypical morphology and an aggressive course of disease. In spite of aggressive treatment including allogeneic hematopoietic stem cell transplantation disease progressed into a rare cutaneous Richter&amp;amp;amp;amp;amp;amp;amp;amp;#39;s syndrome. Trisomy 12 was found as a sole chromosomal change at initial cytogenetic analysis of lymphoma cells. At progression, besides trisomy 12 three concomitant balanced translocations t(2;14)(p13;q32), t(14;19)(q32;q13), and t(18;22)(q21;q11) were found. The same karyotype was confirmed in cells aspirated from skin infiltrates at Richter transformation. Atypical cytological features, trisomy 12, and a progressive course of disease observed in our case are typical for CLL with each of particular Ig translocations that were concomitantly found in CLL for the first time. Similar to &amp;amp;amp;amp;amp;amp;amp;amp;quot;double hit&amp;amp;amp;amp;amp;amp;amp;amp;quot; lymphoma concurrent rearrangements may be relevant also in CLL.

Research paper thumbnail of Selective apoptosis of multiple myeloma cells in primary samples induced by arsenic trioxide

Hematology, 2013

Currently, multiple myeloma (MM) is an incurable disease. Despite the fact that arsenic trioxide ... more Currently, multiple myeloma (MM) is an incurable disease. Despite the fact that arsenic trioxide (ATO) shows promising results in vitro, data from treatment of patients with MM are disappointing. Due to these discrepancies, we compared the efficacy and selectivity of ATO at two different concentrations in samples from MM patients. The extent of apoptosis induced by 2 and 5 µM ATO was evaluated by flow cytometry using annexin V. 34 diagnostic bone marrow samples obtained from MM patients were analysed. 5 µM ATO efficiently induced apoptosis in primary samples. Besides efficacy, also selectivity of action on MM cells in comparison to remaining haematopoietic cells was demonstrated for 5 µM ATO but not for 2 µM ATO. Our study on primary samples confirmed that ATO has a potential role in therapeutic management of MM. Further controlled studies on MM patients are needed.