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    Wyświetlanie 1-14 z 14
    Tytuł:
    The influence of intracellular idarubicin and daunorubicin levels on drug cytotoxicity in childhood acute leukemia.
    Autorzy:
    Styczyński, Jan
    Wysocki, Mariusz
    Dębski, Robert
    Kurylak, Andrzej
    Balwierz, Walentyna
    Rokicka-Milewska, Roma
    Matysiak, Michał
    Balcerska, Anna
    Kowalczyk, Jerzy
    Wachowiak, Jacek
    Sońta-Jakimczyk, Danuta
    Chybicka, Alicja
    Powiązania:
    https://bibliotekanauki.pl/articles/1043814.pdf
    Data publikacji:
    2002
    Wydawca:
    Polskie Towarzystwo Biochemiczne
    Tematy:
    P-glycoprotein
    acute myeloblastic leukemia
    anthracyclines
    acute lymphoblastic leukemia
    drug resistance
    Opis:
    Uptake and efflux of two anthracyclines, idarubicin (IDA) and daunorubicin (DNR), was studied in childhood acute leukemia samples. A comparison of IDA and DNR transport phenomena in relation to drug cytotoxicity and expression of P-glycoprotein (PGP) was made. Intracellular content of IDA/DNR was determined by flow cytometry using the fluorescent properties of the drugs. In vitro drug cytotoxicity was measured by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) assay. PGP expression was analysed by flow cytometry. The uptake and efflux rates were non-significantly higher for IDA than DNR. There were no differences between three types of leukemia with respect to drug content during accumulation and retention. After correction for the cell volume, intracellular concentration of both drugs in each moment of uptake and efflux was significantly lower in relapsed ALL and AML samples in comparison with initial ALL cells. Efflux, but not uptake, of both drugs was inversely correlated with PGP expression and IDA, but not DNR, cytotoxicity. The cytotoxicity was correlated with drug accumulation for both drugs and with drug retention for IDA. In conclusion, it seems that (1) intracellular content was related to the lipophilic properties of the drugs rather than to the type of leukemia, (2) decreased intracellular concentration of both drugs might have an impact on compromised therapy results in AML and relapsed ALL children, (3) IDA presents higher cytotoxicity, which possibly might be decreased by the presence of PGP. These results might have a practical impact on the rational design of new chemotherapy protocols.
    Źródło:
    Acta Biochimica Polonica; 2002, 49, 1; 99-107
    0001-527X
    Pojawia się w:
    Acta Biochimica Polonica
    Dostawca treści:
    Biblioteka Nauki
    Artykuł
    Tytuł:
    Cytotoxic effect of nitric oxide on human hematological malignant cells.
    Autorzy:
    Tsumori, Michihiro
    Tanaka, Junko
    Koshimura, Kunio
    Kawaguchi, Mikiko
    Murakami, Yoshio
    Kato, Yuzuru
    Powiązania:
    https://bibliotekanauki.pl/articles/1043819.pdf
    Data publikacji:
    2002
    Wydawca:
    Polskie Towarzystwo Biochemiczne
    Tematy:
    lymphoma
    myeloma
    leukemia
    nitric oxide
    Opis:
    We investigated the cytotoxic effect of nitric oxide (NO) on primary culture of human hematological malignant cells. Sodium nitroprusside (SNP), an NO donor, had cytotoxic effects on the cells of some patients with malignant lymphoma (ML), acute myelocytic leukemia (AML) or chronic myelomonocytic leukemia (CMMoL), but not with multiple myeloma. Cultured cells from the ML patient remained sensitive to SNP after the cells became resistant to anti-cancer drugs. In contrast, the cells from the patients with AML and CMMoL became resistant to SNP while anti-cancer drugs remained effective. In samples of the cells of the patients with ML and AML, the number of CD3 positive lymphoma cell was decreased by SNP and the number of CD33 negative cells and normal B lymphocytes (CD19 positive cells) were increased. In the cells of the patient with ML, apoptosis was induced by SNP. SNP had no effect on lymphocytes of healthy volunteers. These results suggest that SNP had an anti-tumor effect on human hematological malignant cells.
    Źródło:
    Acta Biochimica Polonica; 2002, 49, 1; 139-144
    0001-527X
    Pojawia się w:
    Acta Biochimica Polonica
    Dostawca treści:
    Biblioteka Nauki
    Artykuł
    Tytuł:
    Preliminary crystallographic studies of Y25F mutant of periplasmic Escherichia coli L-asparaginase.
    Autorzy:
    Kozak, Maciej
    Jaskólski, Mariusz
    Röhm, Klaus
    Powiązania:
    https://bibliotekanauki.pl/articles/1044330.pdf
    Data publikacji:
    2000
    Wydawca:
    Polskie Towarzystwo Biochemiczne
    Tematy:
    protein crystallography
    mutagenesis
    leukemia
    amidohydrolase
    Opis:
    Periplasmic Escherichia coli L-asparaginase II with Y25F mutation in the active-site cavity has been obtained by recombinant techniques. The protein was crystallized in a new hexagonal form (P6522). Single crystals of this polymorph, suitable for X-ray diffraction, were obtained by vapor diffusion using 2-methyl-2,4-pentanediol as precipitant (pH 4.8). The crystals are characterized by a = 81.0, c = 341.1 Å and diffract to 2.45 Å resolution. The asymmetric unit contains two protein molecules arranged into an AB dimer. The physiologically relevant ABA'B' homotetramer is generated by the action of the crystallographic 2-fold axis along [1, -1, 0]. Kinetic studies show that the loss of the phenolic hydroxyl group at position 25 brought about by the replacement of Y with F strongly impairs kcat without significantly affecting Km.
    Źródło:
    Acta Biochimica Polonica; 2000, 47, 3; 807-814
    0001-527X
    Pojawia się w:
    Acta Biochimica Polonica
    Dostawca treści:
    Biblioteka Nauki
    Artykuł
    Tytuł:
    Monocytes in children with leukemias and lymphomas - down-regulation of HLA and costimulatory molecules.
    Autorzy:
    Łuczyński, Włodzimierz
    Stasiak-Barmuta, Anna
    Krawczuk-Rybak, Maryna
    Szymański, Marcin
    Malinowska, Iwona
    Mitura-Lesiuk, Małgorzata
    Powiązania:
    https://bibliotekanauki.pl/articles/1041525.pdf
    Data publikacji:
    2004
    Wydawca:
    Polskie Towarzystwo Biochemiczne
    Tematy:
    infection
    lymphoma
    costimulation
    leukemia
    monocytes
    Opis:
    The aim of the study was to evaluate the function of monocytes in children with leukemias and lymphomas based on the expression of critical costimulatory, activatory and adhesion molecules (CD80, CD86, HLA-DR and CD54 = ICAM-1), estimated with tricolor flow cytometry. In comparison to the control group we found a lower percentage of monocytes with costimulatory molecules (CD80 before and CD86 after lipopolysaccharide stimulation) at the time of diagnosis and of monocytes with HLA-DR molecules after remission induction. We also noted a lower percentage of monocytes with HLA-DR expression in the group with severe or therapy resistant infections. The results of our investigation suggest some defect in costimulation and antigen presentation in lymphoproliferative diseases in children.
    Źródło:
    Acta Biochimica Polonica; 2004, 51, 4; 1067-1073
    0001-527X
    Pojawia się w:
    Acta Biochimica Polonica
    Dostawca treści:
    Biblioteka Nauki
    Artykuł
    Tytuł:
    In vitro activity of oxazaphosphorines in childhood acute leukemia: Preliminary report.
    Autorzy:
    Styczyński, Jan
    Wysocki, Mariusz
    Dębski, Robert
    Balwierz, Walentyna
    Rokicka-Milewska, Roma
    Matysiak, Michał
    Balcerska, Anna
    Kowalczyk, Jerzy
    Wachowiak, Jacek
    Sońta-Jakimczyk, Danuta
    Chybicka, Alicja
    Powiązania:
    https://bibliotekanauki.pl/articles/1043830.pdf
    Data publikacji:
    2002
    Wydawca:
    Polskie Towarzystwo Biochemiczne
    Tematy:
    ALL
    leukemia
    sensitivity
    glufosfamide
    resistance
    Opis:
    Glufosfamide (β-D-glucosyl-ifosfamide mustard) is a new agent for cancer chemotherapy. Its pharmacology is similar to commonly used oxazaphosphorines, but it does not require activation by hepatic cytochrome P-450 and preclinically demonstrates lower nephrotoxicity and myelosuppression than ifosfamide. The aim of the study was a comparison of the drug resistance profiles of glufosfamide and other oxazaphosphorines in childhood acute leukemias. Leukemic cells, taken from children with ALL on diagnosis (n = 41), ALL on relapse (n = 12) and AML on diagnosis (n= 13) were analyzed by means of the MTT assay. The following drugs were tested: glufosfamide (GLU), 4-HOO-ifosfamide (IFO), 4-HOO-cyclophosphamide (CYC) and mafosfamide cyclohexylamine salt (MAF). In the group of initial ALL samples median cytotoxicity values for GLU, IFO, CYC and MAF were 15.5, 33.8, 15.7 and 7.8 μM, respectively. In comparison with initial ALL samples, the relative resistance for GLU and IFO in relapsed ALL samples was 1.9 (p = 0.049) and 1.3 (ns), and in initial AML samples 31 (p < 0.001) and 5 (p = 0.001), respectively. All oxazaphosphorines presented highly significant cross-resistance. Glufosfamide presented high activity against lymphoblasts both on diagnosis and on relapse.
    Źródło:
    Acta Biochimica Polonica; 2002, 49, 1; 221-225
    0001-527X
    Pojawia się w:
    Acta Biochimica Polonica
    Dostawca treści:
    Biblioteka Nauki
    Artykuł
    Tytuł:
    Reversal of drug resistance by silencing Survivin gene expression in acute myeloid leukemia cells
    Autorzy:
    Wu, Yao-Hui
    You, Yong
    Chen, Zhi-Chao
    Zou, Ping
    Powiązania:
    https://bibliotekanauki.pl/articles/1040668.pdf
    Data publikacji:
    2008
    Wydawca:
    Polskie Towarzystwo Biochemiczne
    Tematy:
    chemotherapeutic resistance
    Survivin
    acute myeloid leukemia
    shRNA
    apoptosis
    Opis:
    The role of Survivin in the pathogenesis of leukemia was explored in order to discover the effective avenues for gene therapy. Most primary leukemia cells isolated from patients as well as three leukemia cell lines (HL-60, K562, and U937) all expressed Survivin gene. To investigate the relationship between Survivin and chemotherapeutic resistance, HL-60 cells were treated with daunorubicin (DNR), mitoxantrone (MIT) or arsenious oxide (As2O3), and it was found that after 24 h the level of Survivin mRNA was decreased by 9.7%, 41.0% and 27.5%, respectively. At 72 h, the level of Survivin mRNA was increased by 21.2% and 65.2% in HL-60 cells treated with DNR or MIT, but decreased by 33.2% in those treated with As2O3 as compared with that in the cells treated for 24 h. These results showed that DNR and MIT could initally decrease the expression of Survivin and then increase it, but As2O3 could decrease the Survivin expression continually. Furthermore, shRNA plasmids targeting the Survivin gene (pEGFP-Survivin), which can silence the expression of Survivin with a high specificity, were constructed. pEGFP-Survivin and pEGFP-H1 were transfected into HL-60 cells via electroporation and selected by G418, and HL-60/Survivin and HL-60/EGFP cells were obtained. After treatment with DNR, the cell survival rate and IC50 of DNR in HL-60/Survivin cells were decreased substantially as compared with those of HL-60/EGFP and HL-60 cells (IC50 of DNR: 18.3 ± 2.45 vs 40.8 ± 6.37 and 39.2 ± 5.91 ng/ml, respectively), and the apoptosis rate was elevated ((84.3 ± 19.7)% vs (45.8 ± 13.8)% and (50.9 ± 12.4)%, respectively). These results suggest that shRNA can down-regulate the expression of Survivin in HL-60 cells substantially and improve their sensitivity to DNR. They also further explain the pathogenesis of leukemia drug resistance and provide new theory in the design of clinical therapies.
    Źródło:
    Acta Biochimica Polonica; 2008, 55, 4; 673-680
    0001-527X
    Pojawia się w:
    Acta Biochimica Polonica
    Dostawca treści:
    Biblioteka Nauki
    Artykuł
    Tytuł:
    Influence of BCR/ABL fusion proteins on the course of Ph leukemias.
    Autorzy:
    Telegeev, Gennady
    Dubrovska, Anna
    Dybkov, Mykhaylo
    Maliuta, Stanislav
    Powiązania:
    https://bibliotekanauki.pl/articles/1041568.pdf
    Data publikacji:
    2004
    Wydawca:
    Polskie Towarzystwo Biochemiczne
    Tematy:
    Philadelphia chromosome
    actin cytoskeleton
    leukemia
    BCR/ABL gene
    Opis:
    The hallmark of chronic myeloid leukemia (CML) and a subset of acute lymphoblastic leukemia (ALL) is the presence of the Philadelphia chromosome as a result of the t(9;22) translocation. This gene rearrangement results in the production of a novel oncoprotein, BCR/ABL, a constitutively active tyrosine kinase. There is compelling evidence that the malignant transformation by BCR/ABL is critically dependent on its Abl tyrosine kinase activity. Also the bcr part of the hybrid gene takes part in realization of the malignant phenotype. We supposed that additional mutations accumulate in this region of the BCR/ABL oncogene during the development of the malignant blast crisis in CML patients. In ALL patients having p210 fusion protein the mutations were supposed to be preexisting. Sequencing of PCR product of the BCR/ABL gene (Dbl, PH region) showed that along with single-nucleotide substitutions other mutations, mostly deletions, had occurred. In an ALL patient a deletion of the 5th exon was detected. The size of the deletions varied from 36 to 220 amino acids. For one case of blast crisis of CML changes in the character of actin organization were observed. Taking into account the functional role of these domains in the cell an etiological role of such mutations on the disease phenotype and leukemia progression is plausible.
    Źródło:
    Acta Biochimica Polonica; 2004, 51, 3; 845-849
    0001-527X
    Pojawia się w:
    Acta Biochimica Polonica
    Dostawca treści:
    Biblioteka Nauki
    Artykuł
    Tytuł:
    Mitochondrial mutagenesis in BCR-ABL1-expressing cells sensitive and resistant to imatinib
    Autorzy:
    Blasiak, Janusz
    Hoser, Grazyna
    Bialkowska-Warzecha, Jolanta
    Pawlowska, Elzbieta
    Skorski, Tomasz
    Powiązania:
    https://bibliotekanauki.pl/articles/1038829.pdf
    Data publikacji:
    2016
    Wydawca:
    Polskie Towarzystwo Biochemiczne
    Tematy:
    Imatinib
    chronic myeloid leukemia
    BCR-ABL1 gene
    Opis:
    Imatinib revolutionized the treatment of chronic myeloid leukemia (CML) with the expression of the BCR-ABL1 tyrosine kinase, but imatinib resistance is an emerging problem. Imatinib can hinder the inhibitory effects of BCR-ABL1 on mitochondrial apoptotic pathway, so mitochondrial mutagenesis can be important for its action. To explore the mechanisms of imatinib resistance we created a mouse-derived CML model cells consisting of parental 32D cells (P) and cells transfected with the BCR-ABL1 gene (S cells) or its variants with the Y253H or T315I mutations (253 and 315 cells, respectively), conferring resistance to imatinib. A fraction of the S cells was cultured in increasing concentrations of imatinib, acquiring resistance to this drug (AR cells). The 253, 315 and AR cells, in contrast to S cells, displayed resistance to imatinib. We observed that the T315I cells displayed greater extent of H2O2-induced mtDNA damage than their imatinib-sensitive counterparts. No difference in the sensitivity to UV radiation was observed among all the cell lines. A decrease in the extent of H2O2-induced mtDNA damage was observed during a 120-min repair incubation in all cell lines, but it was significant only in imatinib-sensitive and T315I cells. No difference in the copy number of mtDNA and frequency of the 3,867-bp deletion was observed and genotoxic stress induced by H2O2 or UV did not change this relationship. In conclusion, some aspects of mtDNA mutagenesis, including sensitivity to oxidative stress and DNA repair can contribute to imatinib resistance in BCR-ABL1-expressing cells.
    Źródło:
    Acta Biochimica Polonica; 2016, 63, 2; 365-370
    0001-527X
    Pojawia się w:
    Acta Biochimica Polonica
    Dostawca treści:
    Biblioteka Nauki
    Artykuł
    Tytuł:
    Cytotoxic effects of cladribine and tezacitabine toward HL-60.
    Autorzy:
    Stachnik, Krzysztof
    Grieb, Paweł
    Skierski, Janusz
    Powiązania:
    https://bibliotekanauki.pl/articles/1041452.pdf
    Data publikacji:
    2005
    Wydawca:
    Polskie Towarzystwo Biochemiczne
    Tematy:
    tezacitabine
    cladribine
    flow cytometry
    nucleoside analogs
    leukemia
    HL-60 cells
    Opis:
    The aim of the study was to determine the relation between the cytotoxic and cytostatic effects of tezacitabine and cladribine on a HL-60 cell line and the time of exposure of cells to these drugs. Cell viability and induction of apoptosis were assessed using flow cytometry methods. Apoptosis was confirmed by direct microscopic observation. Growth inhibition was examined by cell counting. After 24 h incubation tezacitabine was equally or less toxic compared to cladribine. However, toxicity of tezacitabine strongly rose after 48 h incubation leading to massive cell death at doses much lower than those of cladribine. Assessment of the effect of increased exposure time on the clinical efficacy of tezacitabine is indicated.
    Źródło:
    Acta Biochimica Polonica; 2005, 52, 2; 561-565
    0001-527X
    Pojawia się w:
    Acta Biochimica Polonica
    Dostawca treści:
    Biblioteka Nauki
    Artykuł
    Tytuł:
    CD40 stimulation induces differentiation of acute lymphoblastic leukemia cells into dendritic cells
    Autorzy:
    Łuczyński, Włodzimierz
    Stasiak-Barmuta, Anna
    Iłendo, Elżbieta
    Krawczuk-Rybak, Maryna
    Malinowska, Iwona
    Mitura-Lesiuk, Małgorzata
    Parfieńczyk, Adam
    Szymański, Marcin
    Powiązania:
    https://bibliotekanauki.pl/articles/1041252.pdf
    Data publikacji:
    2006
    Wydawca:
    Polskie Towarzystwo Biochemiczne
    Tematy:
    immunotherapy
    T-lymphocytes
    CD40L
    acute lymphoblastic leukemia
    dendritic cells
    Opis:
    Despite the very high percentage of long-term remissions in acute lymphoblastic leukemia (ALL) in children, some of them suffer from recurrence of the disease. New treatment modalities, e.g. effective geno- and immunotherapy are needed. The use of neoplasmatic cells to present tumor antigens is one of the approaches in cancer vaccines. ALL cells lack the expression of costimulatory molecules and are poor antigen presenting cells (APCs) for T-cell activation. CD40/40L interaction stimulates B-cells to proliferate, differentiate, upregulate costimulatory molecules and increase antigen presentation. The aim of the study was to test the hypothesis that ALL cells can be turned into professional APCs by CD40L activation. Children with B-cell precursor ALL were enrolled into the study. Mononuclear cells from bone marrow or peripheral blood were stimulated with CD40L and interleukin 4. Results: 1) after culture we noted upregulation of all assessed costimulatory, adhesion and activatory molecules i.e. CD1a, CD11c, CD40, CD54, CD80, CD83, CD86, CD123, HLA class I and II; 2) CD40L activated ALL cells induced proliferation of allogeneic T-cells (measured by [3H]thymidine incorporation). These results confirm the possibility of enhancing the immunogenicity of ALL cells with the CD40L system and indicate that this approach can be used in immunotherapeutic trials.
    Źródło:
    Acta Biochimica Polonica; 2006, 53, 2; 377-382
    0001-527X
    Pojawia się w:
    Acta Biochimica Polonica
    Dostawca treści:
    Biblioteka Nauki
    Artykuł
    Tytuł:
    Cross-resistance to five glucocorticoids in childhood acute lymphoblastic and non-lymphoblastic leukemia samples tested by the MTT assay: Preliminary report.
    Autorzy:
    Styczyński, Jan
    Wysocki, Mariusz
    Dębski, Robert
    Balwierz, Walentyna
    Rokicka-Milewska, Roma
    Matysiak, Michał
    Balcerska, Anna
    Kowalczyk, Jerzy
    Wachowiak, Jacek
    Sońta-Jakimczyk, Danuta
    Chybicka, Alicja
    Powiązania:
    https://bibliotekanauki.pl/articles/1043813.pdf
    Data publikacji:
    2002
    Wydawca:
    Polskie Towarzystwo Biochemiczne
    Tematy:
    cross-resistance
    ALL
    sensitivity
    acute leukemia
    MTT assay
    AML
    glucocorticoid resistance
    Opis:
    In vitro antileukemic activity of five glucocorticoids and their cross-resistance pattern in childhood acute lymphoblastic and non-lymphoblastic leukemia were determined by means of the MTT assay in 25 leukemia cell samples of childhood acute leukemias. The equivalent antileukemic concentrations of the drugs tested were: 34 μM hydrocortisone (HC), 8 μM prednisolone (PRE), 1.5 μM methylprednisolone (MPR), 0.44 μM dexamethasone (DX) and 0.22 μM betamethasone (BET). In comparison with initial ALL cell samples, the relapsed ALL group was more resistant to PRE (38-fold, p = 0.044), DX (> 34-fold, p = 0.04), MPR (38-fold), BET (45-fold) and HC (33-fold). The AML cell samples were even more resistant to: PRE (>85-fold, p=0.001), DX (> 34-fold, p = 0.004), MPR (> 69-fold, p = 0.036), BET (> 69-fold, p = 0.038) and HC (54-fold, p = 0.059) when compared with ALL on initial diagnosis. A significant cross-resistance among all the glucocorticoids used was found. Only in some individual cases the cross-resistance was less pronounced.
    Źródło:
    Acta Biochimica Polonica; 2002, 49, 1; 93-98
    0001-527X
    Pojawia się w:
    Acta Biochimica Polonica
    Dostawca treści:
    Biblioteka Nauki
    Artykuł
    Tytuł:
    Expression of bovine leukemia virus protein p24 in Escherichia coli and its use in the immunoblotting assay.
    Autorzy:
    Bicka, Leokadia
    Kuźmak, Jacek
    Kozaczyńska, Bożena
    Płucienniczak, Andrzej
    Skorupska, Anna
    Powiązania:
    https://bibliotekanauki.pl/articles/1044191.pdf
    Data publikacji:
    2001
    Wydawca:
    Polskie Towarzystwo Biochemiczne
    Tematy:
    bovine leukemia virus
    fusion protein p24
    immunoblotting assay
    gag gene cloning
    Opis:
    The gag gene encoded protein, p24 of bovine leukemia virus (BLV), was cloned and expressed as thioredoxin-6xHis-p24 protein in Escherichia coli. The bacterial cells carrying plasmid pT7THis-p24 expressed the protein of 38 kDa that was detected by immunoblotting analysis using anti-p24 monoclonal antibodies and sera from BLV infected cattle and sheep. The purified p24 fusion protein was shown to be sensitive and specific for detection of BLV antibodies in the infected cattle.
    Źródło:
    Acta Biochimica Polonica; 2001, 48, 1; 227-232
    0001-527X
    Pojawia się w:
    Acta Biochimica Polonica
    Dostawca treści:
    Biblioteka Nauki
    Artykuł
    Tytuł:
    Role of anti-apoptotic pathways activated by BCR/ABL in the resistance of chronic myeloid leukemia cells to tyrosine kinase inhibitors
    Autorzy:
    Danisz, Katarzyna
    Blasiak, Janusz
    Powiązania:
    https://bibliotekanauki.pl/articles/1039432.pdf
    Data publikacji:
    2013
    Wydawca:
    Polskie Towarzystwo Biochemiczne
    Tematy:
    BCR/ABL
    chronic myeloid leukemia
    apoptotic signaling
    tyrosine kinase inhibitor
    imatinib
    drug resistance
    Opis:
    Chronic myeloid leukemia (CML) is a hematological stem cell disorder characterized by the excessive proliferation of the myeloid lineage. In its initial chronic phase, the myeloid progenitor cells expand and demonstrate apparently normal differentiation. The disease may then transform into the accelerated phase, usually associated with resistance to therapy, and finally, into acute leukemic progression phase - blast crisis. Abnormal myeloid cells produce progenitors, which have lost their ability to differentiate, but retain the capacity to proliferate. The molecular hallmark of CML is the Philadelphia chromosome, resulting from reciprocal chromosome translocation, t(9;22)(q34;q11), and containing the BCR/ABL fusion gene, producing the BCR/ABL protein with a constitutive tyrosine kinase activity. BCR/ABL-positive cells have faster growth and proliferation over their normal counterparts and are resistant to apoptosis. Introduction of imatinib (IM), a tyrosine kinase inhibitor, revolutionized the therapy of CML, changing it from a fatal disease into a chronic disorder. However, some patients show a primary resistance to IM, others acquire such resistance in the course of therapy. Therefore, a small number of leukemic stem cells retains self-renewal capacity under IM treatment. Because BCR/ABL is involved in many signaling pathways, some of them may be essential for resistance to IM-induced apoptosis. The PI3K/AKT, Ras and JAK/STAT signaling pathways are involved in resistance to apoptosis and can be activated by BCR/ABL. Therefore, they can be candidates for BCR/ABL-dependent pro-survival pathway(s), allowing a fraction of CML cells to withstand treatment with tyrosine kinase inhibitors.
    Źródło:
    Acta Biochimica Polonica; 2013, 60, 4; 503-514
    0001-527X
    Pojawia się w:
    Acta Biochimica Polonica
    Dostawca treści:
    Biblioteka Nauki
    Artykuł
    Tytuł:
    Reactive oxygen species in BCR-ABL1-expressing cells - relevance to chronic myeloid leukemia
    Autorzy:
    Antoszewska-Smith, Joanna
    Pawlowska, Elzbieta
    Blasiak, Janusz
    Powiązania:
    https://bibliotekanauki.pl/articles/1038675.pdf
    Data publikacji:
    2017
    Wydawca:
    Polskie Towarzystwo Biochemiczne
    Tematy:
    chronic myeloid leukemia
    reactive oxygen species
    DNA damage
    DNA repair
    cancer stem cells
    imatinib resistance
    Opis:
    Chronic myeloid leukemia (CML) results from the t(9;22) reciprocal chromosomal translocation producing the BCR-ABL1 gene, conferring growth and proliferation advantages in the CML cells. CML progresses from chronic, often syndrome-free, to blast phase, fatal if not treated. Although the involvement of BCR-ABL1 in some signaling pathways is considered as the cause of CML, the mechanisms resulting in its progression are not completely known. However, BCR-ABL1 stimulates the production of reactive oxygen species (ROS), which levels increase with CML progression and induce BCR-ABL1 self-mutagenesis. Introducing imatinib and other tyrosine kinase inhibitors (TKIs) to CML therapy radically improved its outcome, but TKIs-resistance became an emerging problem. TKI resistance can be associated with even higher ROS production than in TKI-sensitive cells. Therefore, ROS-induced self-mutagenesis of BCR-ABL1 can be crucial for CML progression and TKI resistance and in this way should be taken into account in therapeutic strategies. As a continuous production of ROS by BCR-ABL1 would lead to its self-destruction and death of CML cells, there must be mechanisms controlling this phenomenon. These can be dependent on DNA repair, which is modulated by BCR-ABL1 and can be different in CML stem and progenitor cells. Altogether, the mechanisms of the involvement of BCR-ABL1 in ROS signaling can be engaged in CML progression and TKI-resistance and warrant further study.
    Źródło:
    Acta Biochimica Polonica; 2017, 64, 1; 1-10
    0001-527X
    Pojawia się w:
    Acta Biochimica Polonica
    Dostawca treści:
    Biblioteka Nauki
    Artykuł
      Wyświetlanie 1-14 z 14

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