Research Topics
Genomes and Genes
| Tomasz SkorskiSummaryAffiliation: Temple University Country: USA Publications
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Detail Information
Publications
Oncogenic tyrosine kinases and the DNA-damage responseTomasz Skorski
Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, Pennsylvania 19122, USA
Nat Rev Cancer 2:351-60. 2002..So, what are the mechanisms involved, and what is the potential for overcoming OTK-mediated resistance in the clinic?..
BCR/ABL regulates response to DNA damage: the role in resistance to genotoxic treatment and in genomic instabilityTomasz Skorski
Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, Pennsylvania, PA 19122, USA
Oncogene 21:8591-604. 2002..Inhibition of BCR/ABL kinase activity by STI571 (Gleevec, imatinib mesylate) reverses drug resistance and, in combination with standard chemotherapeutics can exert strong anti-leukemia effect...
ATR-Chk1 axis protects BCR/ABL leukemia cells from the lethal effect of DNA double-strand breaksMargaret Nieborowska-Skorska
Department of Microbiology and Immunology, Temple University, Philadelphia, Pennsylvania 19140, USA
Cell Cycle 5:994-1000. 2006..In conclusion, ATR-Chk1 axis was strongly activated in BCR/ABL-positive cells and contributed to the resistance to DNA cross-linking agents causing numerous replication-dependent DSBs...
Enhanced phosphorylation of Nbs1, a member of DNA repair/checkpoint complex Mre11-RAD50-Nbs1, can be targeted to increase the efficacy of imatinib mesylate against BCR/ABL-positive leukemia cellsLori Rink
Department of Microbiology and Immunology, Temple University, Philadelphia, PA 19140, USA
Blood 110:651-60. 2007..Interestingly, inhibition of Nbs1 phosphorylation by S343A mutant enhanced the antileukemia effect of the combination of imatinib and genotoxic agent...
Intrinsic regulation of the interactions between the SH3 domain of p85 subunit of phosphatidylinositol-3 kinase and the protein network of BCR/ABL oncogenic tyrosine kinaseShu Yue Ren
Center for Biotechnology, College of Science and Technology, Temple University, 1900 N 12th St, Philadelphia, PA 19122, USA
Exp Hematol 33:1222-8. 2005..Therefore, we made an attempt to better characterize p85alpha-BCR/ABL interactions...
T-antigen of the human polyomavirus JC attenuates faithful DNA repair by forcing nuclear interaction between IRS-1 and Rad51Joanna Trojanek
Center for Neurovirology and Cancer Biology, College of Science and Technology, Temple University, Biology Life Science Building, Philadelphia, Pennsylvania 19122, USA
J Cell Physiol 206:35-46. 2006..Our observations define a new mechanism by which viral protein utilizes cytosolic molecule to inhibit faithful DNA repair, and suggest how polyomaviruses could compromise stability of the genome. (c) 2005 Wiley-Liss, Inc...
BCR/ABL kinase induces self-mutagenesis via reactive oxygen species to encode imatinib resistanceMateusz Koptyra
Department of Microbiology and Immunology, School of Medicine and the Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA 19140, USA
Blood 108:319-27. 2006..Simultaneous administration of IM and an antioxidant exerted better antimutagenic effect than an antioxidant alone. Therefore, inhibition of ROS should diminish mutagenesis and enhance the effectiveness of IM...
BCR/ABL inhibits mismatch repair to protect from apoptosis and induce point mutationsTomasz Stoklosa
Department of Microbiology and Immunology, Temple University, Philadelphia, Pennsylvania 19140, USA
Cancer Res 68:2576-80. 2008..In conclusion, these results suggest that BCR/ABL kinase abrogates MMR activity to inhibit apoptosis and induce mutator phenotype...
BLM helicase is activated in BCR/ABL leukemia cells to modulate responses to cisplatinArtur Slupianek
Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA 19122, USA
Oncogene 24:3914-22. 2005..These data suggest that BLM collaborates with RAD51 to facilitate HRR and promotes the resistance of BCR/ABL-positive leukemia cells to DNA-damaging agents...
BCR/ABL modifies the kinetics and fidelity of DNA double-strand breaks repair in hematopoietic cellsArtur Slupianek
Center for Biotechnology, College of Science and Technology, Temple University, Bio Life Sciences Building, Room 419, 1900 N 12th Street, Philadelphia, PA 19122, USA
DNA Repair (Amst) 5:243-50. 2006..We propose that unfaithful repair of DSBs may contribute to genomic instability in the Philadelphia chromosome-positive leukemias...
BCR/ABL recruits p53 tumor suppressor protein to induce drug resistanceTomasz Stoklosa
Molecular Carcinogenesis Section, Center of Biotechnology, College of Science and Technology, Temple University, 1900 N. 12th Street, Philadelphia, Pennsylvania 19122, USA
Cell Cycle 3:1463-72. 2004..In conclusion, accumulation of the p53 protein contributed to prolonged G(2)/M checkpoint activation and drug resistance in myeloid cells expressing the BCR/ABL oncoproteins...
BCR/ABL stimulates WRN to promote survival and genomic instabilityArtur Slupianek
Department of Microbiology and Immunology, School of Medicine, Temple University, Philadelphia, Pennsylvania 19140, USA
Cancer Res 71:842-51. 2011..In summary, we postulate that BCR/ABL-mediated stimulation of WRN modulates the efficiency and fidelity of major DSB repair mechanisms to protect leukemia cells from apoptosis and to facilitate genomic instability...
Impaired homologous recombination DNA repair and enhanced sensitivity to DNA damage in prostate cancer cells exposed to anchorage-independenceJin Ying Wang
1Center for Neurovirology and Cancer Biology, College of Science and Technology, Temple University, 1900 North 12th Street, Biology Life Science Building, Philadelphia, PA 19122, USA
Oncogene 24:3748-58. 2005..This temporal attenuation of HRR may contribute to the accumulation mutations after DNA damage, and possibly the selection of new adaptations in cells, which survived genotoxic treatment...
NPM/ALK downregulates p27Kip1 in a PI-3K-dependent mannerArtur Slupianek
College of Science and Technology, Center for Biotechnology, Temple University, Philadelphia, PA 19008, USA
Exp Hematol 32:1265-71. 2004..It was reported that p27Kip1 function is impaired in many tumors. In this study we investigated the role of PI-3K/AKT in NPM/ALK-dependent downregulation of p27Kip1 protein...
Rac2-MRC-cIII-generated ROS cause genomic instability in chronic myeloid leukemia stem cells and primitive progenitorsMargaret Nieborowska-Skorska
Department of Microbiology and Immunology, Temple University School of Medicine, 3400 N Broad Street, Philadelphia, PA 19140, USA
Blood 119:4253-63. 2012..We postulate that the Rac2-MRC-cIII pathway triggers ROS-mediated genomic instability in LSCs and primitive LPCs, which could be targeted to prevent the relapse and malignant progression of CML...
HIV-1 Tat increases cell survival in response to cisplatin by stimulating Rad51 gene expressionGalina Chipitsyna
Center for Neurovirology and Cancer Biology, College of Science and Technology, Temple University, 1900 North 12th Street, 015 96, Philadelphia, PA 19122, USA
Oncogene 23:2664-71. 2004..These observations ascribe a new role for Tat in host genomic integrity, perhaps by affecting the expression of genes involved in DNA repair...
Genomic instability: The cause and effect of BCR/ABL tyrosine kinaseTomasz Skorski
Department of Microbiology and Immunology, School of Medicine, Temple University, MRB 548A, 3400 N Broad Street, Philadelphia, PA 19140, USA
Curr Hematol Malig Rep 2:69-74. 2007..Therefore, chronic myelogenous leukemia cells display mutator phenotype...
Targeting RAD51 phosphotyrosine-315 to prevent unfaithful recombination repair in BCR-ABL1 leukemiaArtur Slupianek
Department of Microbiology and Immunology, School of Medicine, Temple University, Philadelphia, PA, USA
Blood 118:1062-8. 2011..In conclusion, we postulate that BCR-ABL1 kinase-mediated RAD51(pY315) promotes unfaithful HomeoRR in leukemia cells, which may contribute to accumulation of secondary chromosomal aberrations responsible for CML relapse and progression...
The Src family kinase Hck couples BCR/ABL to STAT5 activation in myeloid leukemia cellsAgata Klejman
Center of Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA 19122, USA
EMBO J 21:5766-74. 2002..These data identify a novel BCR/ABL-Hck-STAT5 signaling pathway, which plays an important role in BCR/ABL-mediated transformation of myeloid cells...
BCR-ABL1 kinase facilitates localization of acetylated histones 3 and 4 on DNA double-strand breaksRafal Falinski
Department of Microbiology and Immunology, School of Medicine, Temple University, Philadelphia, PA 19140, USA
Leuk Res 36:241-4. 2012....
BCR/ABL and other kinases from chronic myeloproliferative disorders stimulate single-strand annealing, an unfaithful DNA double-strand break repairKimberly Cramer
Department of Microbiology and Immunology, Temple University, Philadelphia, Pennsylvania 19140, USA
Cancer Res 68:6884-8. 2008..Taken together, these findings suggest a role of FTKs in causing disease progression in MPDs by inducing chromosomal instability through the production of DSBs and stimulation of SSA repair...
Id1 transcription inhibitor-matrix metalloproteinase 9 axis enhances invasiveness of the breakpoint cluster region/abelson tyrosine kinase-transformed leukemia cellsMargaret Nieborowska-Skorska
Department of Microbiology and Immunology, School of Medicine, Temple University, Philadelphia, Pennsylvania 19140, USA
Cancer Res 66:4108-16. 2006..These data suggest that BCR/ABL-STAT5-Id1-MMP9 pathway may play a critical role in BCR/ABL-mediated leukemogenesis by enhancing invasiveness of leukemia cells...
BCR/ABL oncogenic kinase promotes unfaithful repair of the reactive oxygen species-dependent DNA double-strand breaksMichal O Nowicki
Center for Biotechnology, College of Science and Technology, Temple University, Bio-Life Sciences Bldg, Rm 419, 1900 N 12th St, Philadelphia, PA 19122, USA
Blood 104:3746-53. 2004..We propose that the following series of events may contribute to genomic instability of Ph-positive leukemias: BCR/ABL --> ROSs --> oxidative DNA damage --> DSBs in proliferating cells --> unfaithful HRR and NHEJ repair...
Genetic mechanisms of chronic myeloid leukemia blastic transformationTomasz Skorski
Department of Microbiology and Immunology, School of Medicine, Temple University, Philadelphia, PA 19140, USA
Curr Hematol Malig Rep 7:87-93. 2012..CML-BP responds poorly to treatment and is usually fatal. This review discusses the role of genomic instability leading to blastic transformation of CML and proposes some novel therapeutic approaches...
Chronic myeloid leukemia cells refractory/resistant to tyrosine kinase inhibitors are genetically unstable and may cause relapse and malignant progression to the terminal disease stateTomasz Skorski
Department of Microbiology and Immunology, School of Medicine, Temple University, Philadelphia, Pennsylvania 19140, USA
Leuk Lymphoma 52:23-9. 2011....
Phosphatidylinositol 3-kinase p85{alpha} subunit-dependent interaction with BCR/ABL-related fusion tyrosine kinases: molecular mechanisms and biological consequencesShu Yue Ren
Molecular Carcinogenesis Section, Center for Biotechnology, College of Science and Technology, Temple University, BLSB 419, 1900 N 12th Street, Philadelphia, PA 19122, USA
Mol Cell Biol 25:8001-8. 2005..In conclusion, we have identified the domains of p85alpha responsible for the interaction with the FTK protein network and transduction of leukemogenic signaling...
Role of the insulin-like growth factor I/insulin receptor substrate 1 axis in Rad51 trafficking and DNA repair by homologous recombinationJoanna Trojanek
Center for Neurovirology and Cancer Biology, College of Science and Technology, Temple University, Philadelphia, Pennsylvania 19122, USA
Mol Cell Biol 23:7510-24. 2003..These results point to a direct role of IRS-1 in HRR and suggest a novel role for the IGF-IR/IRS-1 axis in supporting the stability of the genome...
BCR/ABL, DNA damage and DNA repair: implications for new treatment conceptsTomasz Skorski
Department of Microbiology and Immunology, Temple University, Philadelphia, PA 19140, USA
Leuk Lymphoma 49:610-4. 2008..Possible benefits of anti-mutagenic therapy used in pursuing the cure of BCR/ABL-positive leukemias are discussed...
Phosphatidylinositol-3 kinase inhibitors enhance the anti-leukemia effect of STI571Agata Klejman
Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, Pennsylvania 19122, USA
Oncogene 21:5868-76. 2002..In conclusion, combination of STI571+WT or STI571+LY may represent a novel approach against the Ph(1)-positive leukemias...
[Uracil-DNA glycosylases]Dariusz Pytel
Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, USA
Postepy Biochem 54:362-70. 2008..UNG2, MBD4 and TDG glycosylases may cooperate with mismatch repair proteins and TDG can be involved in nucleotide excision repair system...
Complementary functions of the antiapoptotic protein A1 and serine/threonine kinase pim-1 in the BCR/ABL-mediated leukemogenesisMalgorzata Nieborowska-Skorska
Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA 19122, USA
Blood 99:4531-9. 2002..These data indicate that induction of A1 and pim-1 expression may play a critical role in the BCR/ABL-dependent transformation...
Chronic myelogenous leukemia molecular signatureMichal Oskar Nowicki
Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA 19122, USA
Oncogene 22:3952-63. 2003..Altogether, this work provides a large body of information regarding gene expression profiles associated with CML and also represents a source of potential targets for CML therapeutics...
Fusion tyrosine kinases induce drug resistance by stimulation of homology-dependent recombination repair, prolongation of G(2)/M phase, and protection from apoptosisArtur Slupianek
Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, Pennsylvania 19122, USA
Mol Cell Biol 22:4189-201. 2002..Thus, we postulate that RAD51-dependent facilitation of DSB repair, antiapoptotic activity of Bcl-xL, and delay in progression through the G(2)/M phase work in concert to induce drug resistance in FTK-positive leukemias and lymphomas...
Multilevel dysregulation of STAT3 activation in anaplastic lymphoma kinase-positive T/null-cell lymphomaQian Zhang
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
J Immunol 168:466-74. 2002..These results also suggest that activated STAT3, which is known to display oncogenic properties, as well as its regulatory molecules may represent attractive targets for novel therapies in ALK+ TCL...
Fusion oncogenic tyrosine kinases alter DNA damage and repair after genotoxic treatment: role in drug resistance?Grazyna Hoser
Department of Clinical Cytobiology, Medical Center for Postgraduate Education, 01 813 Warszawa, Marymoncka 99, Poland
Leuk Res 27:267-73. 2003..We hypothesize that facilitation of the DNA repair in FTK-positive cells may contribute to their resistance to genotoxic treatment...
Imatinib mesylate (STI571) abrogates the resistance to doxorubicin in human K562 chronic myeloid leukemia cells by inhibition of BCR/ABL kinase-mediated DNA repairIreneusz Majsterek
Department of Molecular Genetics, University of Lodz, Banacha 12 16 Street, 90 237 Lodz, Poland
Mutat Res 603:74-82. 2006..The results suggest that STI571-mediated inhibition of BCR/ABL kinase activity can affect the effectiveness of the DNA-repair pathways, which in turn may enhance drug sensitivity of leukemia cells...
The role of focal adhesion kinase in the emigration of cells from confluent culturesHalina Trembacz
Department of Cell Biology, Cancer Center, , W.K. Roentgen 5, 02-781Warsaw, Poland
Cell Mol Biol Lett 7:1047-57. 2002..In conclusion, it can be postulated that FAK plays an important role in the mechanism of contact inhibition...
TEL/JAK2 tyrosine kinase inhibits DNA repair in the presence of amifostineEwa Gloc
Department of Molecular Genetics, , Poland
Acta Biochim Pol 49:121-8. 2002..Moreover, TEL/JAK2 tyrosine kinase might be involved in cellular response to DNA damage. Amifostine could promote apoptosis or lower the threshold for apoptosis induction dependent on TEL/JAK2 activation...
STI571 reduces NER activity in BCR/ABL-expressing cellsTomasz Sliwinski
Department of Molecular Genetics, University of Lodz, Banacha 12 16, 90 237 Lodz, Poland
Mutat Res 654:162-7. 2008..Therefore, STI571 may overcome the drug resistance associated with increased DNA repair in BCR/ABL-positive leukemias...
p210 BCR/ABL kinase regulates nucleotide excision repair (NER) and resistance to UV radiationYvan Canitrot
Genetic Instability and Cancer, Institut de Pharmacologie et Biologie Structurale, Toulouse, France
Blood 102:2632-7. 2003..In contrast, p210 BCR/ABL expression in myeloid cells facilitated NER and induced resistance to UV...
