Research Topics
| D PerrottiSummaryAffiliation: The Ohio State University Country: USA Publications
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Publications
Protein phosphatase 2A: a target for anticancer therapyDanilo Perrotti
Human Cancer Genetics Program, Department of Molecular Virology, Immunology, and Medical Genetics, and Comprehensive Cancer Center, Ohio State University, Columbus, OH, USA Electronic address
Lancet Oncol 14:e229-38. 2013..Here, we discuss PP2A as a druggable tumour suppressor in view of the possible introduction of PP2A-activating drugs into anticancer therapeutic protocols...
ReSETting PP2A tumour suppressor activity in blast crisis and imatinib-resistant chronic myelogenous leukaemiaD Perrotti
Human Cancer Genetics Program, Department of Molecular Virology, Immunology and Medical Genetics, and the Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA
Br J Cancer 95:775-81. 2006..Thus, the combination of PP2A phosphatase-activating and BCR/ABL kinase-inhibiting drugs may represent a powerful therapeutic strategy for blast crisis CML patients...- Protein phosphatase 2A (PP2A), a drugable tumor suppressor in Ph1(+) leukemiasDanilo Perrotti
Human Cancer Genetics Program, Department of Molecular Virology, Immunology and Medical Genetics, and Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA
Cancer Metastasis Rev 27:159-68. 2008..Herein, we review current knowledge of PP2A biology and function with particular emphasis on its tumor suppressor activity and possible therapeutic implications in cancer... - BCR-ABL1 kinase-dependent alteration of mRNA metabolism: potential alternatives for therapeutic interventionDanilo Perrotti
Human Cancer Genetics Program, Depatment of Molecular Virology, Immunology and Medical Genetics, Comprehensive Cancer Center and Center for RNA Biology, The Ohio State University, Columbus, OH 43210 2207, USA
Leuk Lymphoma 52:30-44. 2011.... 
From mRNA metabolism to cancer therapy: chronic myelogenous leukemia shows the wayDanilo Perrotti
The Molecular Biology and Cancer Genetics Program, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43240, USA
Clin Cancer Res 13:1638-42. 2007....- Chronic myeloid leukemia: mechanisms of blastic transformationDanilo Perrotti
Department of Molecular Virology, Immunology and Medical Genetics and Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 41230, USA
J Clin Invest 120:2254-64. 2010..The latter responds poorly to treatment and is usually fatal. Here, we discuss what is known about the molecular mechanisms leading to blastic transformation of CML and propose some novel therapeutic approaches... - The tumor suppressor PP2A is functionally inactivated in blast crisis CML through the inhibitory activity of the BCR/ABL-regulated SET proteinPaolo Neviani
Human Cancer Genetics Program, Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, Columbus, Ohio 43210, USA
Cancer Cell 8:355-68. 2005..Thus, functional inactivation of PP2A is essential for BCR/ABL leukemogenesis and, perhaps, required for blastic transformation... - Interplay of RUNX1/MTG8 and DNA methyltransferase 1 in acute myeloid leukemiaShujun Liu
Divisions of Hematology Oncology, Department of Internal Medicine and the Comprehensive Cancer Center, Ohio State University, Columbus, Ohio, USA
Cancer Res 65:1277-84. 2005..These results suggest a novel mechanism for gene silencing mediated by RUNX1/MTG8 and support the combination of HDAC and DNMT inhibitors as a novel therapeutic approach for t(8;21) AML... - Hlx homeobox transcription factor negatively regulates interferon-gamma production in monokine-activated natural killer cellsBrian Becknell
Medical Scientist Program, Department of Internal Medicine, College of Medicine and Public Health, The Ohio State University, Columbus, OH 43210, USA
Blood 109:2481-7. 2007..Thus, Hlx expression in activated NK cells temporally controls and limits the monokine-induced production of IFN-gamma, in part through the targeted depletion of STAT4... - Modulation of DNA methylation by a sesquiterpene lactone parthenolideZhongfa Liu
Division of Pharmaceutics, Colleges of Pharmacy, The Ohio State University, Columbus, OH 43210, USA
J Pharmacol Exp Ther 329:505-14. 2009..Hence, our study established parthenolide as an effective DNA methylation inhibitor, representing a novel prototype for DNMT1 inhibitor discovery and development from natural structural-diversified sesquiterpene lactones... - MicroRNA-29b induces global DNA hypomethylation and tumor suppressor gene reexpression in acute myeloid leukemia by targeting directly DNMT3A and 3B and indirectly DNMT1Ramiro Garzon
Department of Medicine, Ohio State University, Columbus, 43210, USA
Blood 113:6411-8. 2009.... - Downregulation of p53-inducible microRNAs 192, 194, and 215 impairs the p53/MDM2 autoregulatory loop in multiple myeloma developmentFlavia Pichiorri
Department of Molecular Virology, Comprehensive Cancer Center, Ohio State University, Columbus, 43210, USA
Cancer Cell 18:367-81. 2010..The results suggest that these miRNAs are positive regulators of p53 and that their downregulation plays a key role in MM development... - The PP2A inhibitor SET regulates natural killer cell IFN-gamma productionRossana Trotta
Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, Columbus, OH 43210, USA
J Exp Med 204:2397-405. 2007..Thus, SET expression is essential for suppressing PP2A phosphatase activity that would otherwise limit NK cell antitumoral and/or antiinflammatory functions by impairing NK cell production of IFN-gamma... - Sp1/NFkappaB/HDAC/miR-29b regulatory network in KIT-driven myeloid leukemiaShujun Liu
Division of Hematology Oncology, The Ohio State University, Columbus, OH 43210, USA
Cancer Cell 17:333-47. 2010.... - Bortezomib induces DNA hypomethylation and silenced gene transcription by interfering with Sp1/NF-kappaB-dependent DNA methyltransferase activity in acute myeloid leukemiaShujun Liu
Division of Hematology Oncology, The Ohio State University, Columbus, OH 43210, USA
Blood 111:2364-73. 2008..Our results unveil the Sp1/NF-kappaB pathway as a modulator of DNA methyltransferase activity in human cancer and identify bortezomib as a novel epigenetic-targeting drug... - The PP2A inhibitor SET regulates granzyme B expression in human natural killer cellsRossana Trotta
Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University Comprehensive Cancer Center, 460 West 12th Ave, Columbus, OH 43210, USA
Blood 117:2378-84. 2011..These data provide evidence that granzyme B gene expression and therefore human NK-cell cytotoxicity can be regulated by the PP2A-SET interplay... - miR-328 functions as an RNA decoy to modulate hnRNP E2 regulation of mRNA translation in leukemic blastsAnna M Eiring
Human Cancer Genetics Program, Department of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University, Columbus, OH 43210, USA
Cell 140:652-65. 2010..Altogether, these data reveal the dual ability of a microRNA to control cell fate both through base pairing with mRNA targets and through a decoy activity that interferes with the function of regulatory proteins... - TGF-beta utilizes SMAD3 to inhibit CD16-mediated IFN-gamma production and antibody-dependent cellular cytotoxicity in human NK cellsRossana Trotta
Department of Molecular Virology, Immunology, and Medical Genetics, Ohio State University, Columbus, OH 43210, USA
J Immunol 181:3784-92. 2008..This effect was accentuated in cells overexpressing SMAD3. Collectively, our results indicate that TGF-beta inhibits CD16-mediated human NK cell IFN-gamma production and ADCC, and these effects are mediated via SMAD3... - Stem cell factor and interleukin-2/15 combine to enhance MAPK-mediated proliferation of human natural killer cellsDon M Benson
Division of Hematology Oncology, The Ohio State University, Columbus, OH 43210 1240, USA
Blood 113:2706-14. 2009..The effect results at least in part via enhanced MAPK-mediated modulation of p27 and CDK4. Collectively the data reveal a novel mechanism by which SCF enhances cellular proliferation in combination with IL-2/15 in primary human NK cells... - Characterization of in vitro and in vivo hypomethylating effects of decitabine in acute myeloid leukemia by a rapid, specific and sensitive LC-MS/MS methodZhongfa Liu
College of Pharmacy, The Ohio State University, Columbus, Ohio 43210, USA
Nucleic Acids Res 35:e31. 2007..Our data support the use of our LC-MS/MS method for clinical pharmacodynamic determination of changes in GDM in vivo... - Identification of novel posttranscriptional targets of the BCR/ABL oncoprotein by ribonomics: requirement of E2F3 for BCR/ABL leukemogenesisAnna M Eiring
Human Cancer Genetics Program, Department of Molecular Virology, Immunology and Medical Genetics and Comprehensive Cancer Center, Ohio State University, Columbus, USA
Blood 111:816-28. 2008..Thus, the complexity of the mRNA/RBP network, together with the discovery of E2F3 as an hnRNP-A1-regulated factor, outlines the relevant role played by RBPs in posttranscriptional regulation of CML development and progression... - Targeting AML1/ETO-histone deacetylase repressor complex: a novel mechanism for valproic acid-mediated gene expression and cellular differentiation in AML1/ETO-positive acute myeloid leukemia cellsShujun Liu
Division of Hematology, The Ohio State University, 320 West 10th Avenue, Columbus, OH 43210, USA
J Pharmacol Exp Ther 321:953-60. 2007.... - Src homology 2 domain-containing inositol-5-phosphatase and CCAAT enhancer-binding protein beta are targeted by miR-155 in B cells of Emicro-MiR-155 transgenic miceStefan Costinean
Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA
Blood 114:1374-82. 2009..We hypothesize that miR-155, by down-modulating Ship and C/EBPbeta, initiates a chain of events that leads to the accumulation of large pre-B cells and acute lymphoblastic leukemia/high-grade lymphoma... - Adverse prognostic significance of KIT mutations in adult acute myeloid leukemia with inv(16) and t(8;21): a Cancer and Leukemia Group B StudyPeter Paschka
Division of Hematology and Oncology, Department of Internal Medicine, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA
J Clin Oncol 24:3904-11. 2006..We suggest that patients with core-binding factor AML should be screened for mutKIT at diagnosis for both prognostic and therapeutic purposes, given that activated KIT potentially can be targeted with novel tyrosine kinase inhibitors... - A MAPK/HNRPK pathway controls BCR/ABL oncogenic potential by regulating MYC mRNA translationMario Notari
Human Cancer Genetics Program, The Ohio State University Medical Center, Columbus, OH 43240, USA
Blood 107:2507-16. 2006..Thus, BCR/ABL-dependent enhancement of HNRPK translation-regulation is important for BCR/ABL leukemogenesis and, perhaps, it might contribute to blast crisis transformation... - Translational regulation by the p210 BCR/ABL oncoproteinDanilo Perrotti
Human Cancer Genetics Program, Department of Molecular Virology, Immunology and Medical Genetics and the Comprehensive Cancer Center, The Ohio State University, Columbus OH 43210, USA
Oncogene 23:3222-9. 2004..The identification of mRNA targets translationally regulated by RNA binding proteins overexpressed in tumor cells may lead to the development of therapeutic strategies aimed at modulating the translation rate of specific mRNAs... - FTY720, a new alternative for treating blast crisis chronic myelogenous leukemia and Philadelphia chromosome-positive acute lymphocytic leukemiaPaolo Neviani
Human Cancer Genetics Program, Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, Columbus, Ohio, USA
J Clin Invest 117:2408-21. 2007..Altogether, these results highlight the therapeutic relevance of rescuing PP2A tumor suppressor activity in Ph1 leukemias and strongly support the introduction of the PP2A activator FTY720 in the treatment of CML-BC and Ph1 ALL patients... - Understanding the molecular basis of imatinib mesylate therapy in chronic myelogenous leukemia and the related mechanisms of resistance. Commentary re: A. N. Mohamed et al., The effect of imatinib mesylate on patients with Philadelphia chromosome-positiveGuido Marcucci
Division of Hematology and Oncology, Department of Internal Medicine, The James Cancer Hospital and The Comprehensive Cancer Center at The Ohio State University, Columbus, Ohio 43210, USA
Clin Cancer Res 9:1248-52. 2003 - FTY720 demonstrates promising preclinical activity for chronic lymphocytic leukemia and lymphoblastic leukemia/lymphomaQing Liu
Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, OH, USA
Blood 111:275-84. 2008..These results provide the first evidence for the potential use of FTY720 as a therapeutic agent in a variety of B-cell malignancies, including CLL... - Overexpression of the ETS-related gene, ERG, predicts a worse outcome in acute myeloid leukemia with normal karyotype: a Cancer and Leukemia Group B studyGuido Marcucci
Division of Hematology and Oncology, Department of Internal Medicine, Comprehensive Cancer Center, The Ohio State University, Columbus OH 43210, USA
J Clin Oncol 23:9234-42. 2005..To test the prognostic significance of ETS-related gene (ERG) expression in cytogenetically normal primary acute myeloid leukemia (AML)... - Altered mRNA translation: possible mechanism for CML disease progressionDanilo Perrotti
Division of Human Cancer Genetics, Ohio State University, 440 Tzagournis Medical Research Bldg, 420 W. 12 Avenue, Columbus, OH 43210, USA
Cell Cycle 2:177-80. 2003 - Efficient delivery of a Bcl-2-specific antisense oligodeoxyribonucleotide (G3139) via transferrin receptor-targeted liposomesShih-Jiuan Chiu
Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA
J Control Release 112:199-207. 2006..8 microM to 0.18 microM. In conclusion, Tf-conjugated liposomes are effective delivery vehicles for G3139 antisense oligos in TfR positive K562 cells and warrant further investigation as an in vivo oligo delivery vehicle... - Novel c-CBL and CBL-b ubiquitin ligase mutations in human acute myeloid leukemiaMichael A Caligiuri
Integrated Biomeducal Graduate Program, Comprehensive Cancer Center, Ohio State University, Columbus, OH 23240, USA
Blood 110:1022-4. 2007..Short-interfering RNA knockdown of mutant c-CBL present in MOLM-13 cells was growth inhibitory. In summary, novel mutations in c-CBL and CBL-b have been identified in human AML and may represent potential targets for novel therapeutics... - High levels of the BCR/ABL oncoprotein are required for the MAPK-hnRNP-E2 dependent suppression of C/EBPalpha-driven myeloid differentiationJi Suk Chang
Human Cancer Genetics Program, Department of Molecular Virology, Immunology and Medical Genetics, Ohio State University, Columbus, OH 23240, USA
Blood 110:994-1003. 2007..Furthermore, these findings suggest the inclusion of clinically relevant MAPK inhibitors in the therapy of CML-BC... - BCR/ABL activates mdm2 mRNA translation via the La antigenRossana Trotta
Department of Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson Medical College, Philadelphia, PA 19107, USA
Cancer Cell 3:145-60. 2003..By contrast, La overexpression led to increased MDM2 levels and enhanced resistance to apoptosis. Thus, La-dependent activation of mdm2 translation might represent an important molecular mechanism involved in BCR/ABL leukemogenesis... - BCR-ABL suppresses C/EBPalpha expression through inhibitory action of hnRNP E2Danilo Perrotti
Department of Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
Nat Genet 30:48-58. 2002..Our results indicate that BCR-ABL regulates the expression of C/EBPalpha by inducing hnRNP E2-which inhibits the translation of CEBPA mRNA... - Post-transcriptional mechanisms in BCR/ABL leukemogenesis: role of shuttling RNA-binding proteinsDanilo Perrotti
Thomas Jefferson University, Department of Microbiology and Immunology, Kimmel Cancer Institute, Philadelphia, PA 19107, USA
Oncogene 21:8577-83. 2002..The identification of the mRNA subsets associated with RNA-binding proteins upregulated in BCR/ABL-expressing cells should functionally link the process of leukemogenesis with alteration of mRNA metabolism... - CCAAT/Enhancer binding proteins repress the leukemic phenotype of acute myeloid leukemiaBao Tran H Truong
Comprehensive Cancer Center and Department of Laboratory Medicine, University of California, San Francisco 94143 0128, USA
Blood 101:1141-8. 2003..Our results support the hypothesis that induction of C/EBP activity is a critical effect of tRA in APL. Furthermore, our findings suggest that targeted modulation of C/EBP activities could provide a new approach to therapy of AML... - Loss of C/EBP alpha and favorable prognosis of acute myeloid leukemias: a biological paradoxDanilo Perrotti
J Clin Oncol 22:582-4. 2004 - The biology of CML blast crisisBruno Calabretta
Department of Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson Medical College, Philadelphia, PA 19107, USA
Blood 103:4010-22. 2004.... - CDDO induces granulocytic differentiation of myeloid leukemic blasts through translational up-regulation of p42 CCAAT enhancer binding protein alphaSteffen Koschmieder
Department of Medicine, Hematology and Oncology, University of Munster, Münster Germany
Blood 110:3695-705. 2007..Because AML is characterized by arrested differentiation, our data suggest the inclusion of CDDO in the therapy of AML characterized by dysfunctional CEBPA expression... - Inducible activation of CEBPB, a gene negatively regulated by BCR/ABL, inhibits proliferation and promotes differentiation of BCR/ABL-expressing cellsClara Guerzoni
Department of Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson Medical College, 233 South and 10th Street, Philadelphia, PA 19107, USA
Blood 107:4080-9. 2006.... - CCAAT/enhancer binding proteins alpha and epsilon cooperate with all-trans retinoic acid in therapy but differ in their antileukemic activitiesYoung Jin Lee
Dept of Laboratory Medicine, Box 0134, 513 Parnassus Ave, San Francisco, CA 94143, USA
Blood 108:2416-9. 2006..We also show that forced expression of C/EBPalpha or C/EBPepsilon in combination with ATRA treatment has a synergistic effect on survival of leukemic mice compared with either therapy alone... - Rac guanosine triphosphatases represent integrating molecular therapeutic targets for BCR-ABL-induced myeloproliferative diseaseEmily K Thomas
Division of Experimental Hematology, Cincinnati Children s Research Foundation, Cincinnati Children s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA
Cancer Cell 12:467-78. 2007..These data demonstrate that Rac is an additional therapeutic target in p210-BCR-ABL-mediated MPD... - NPM/ALK binds and phosphorylates the RNA/DNA-binding protein PSF in anaplastic large-cell lymphomaAnnamaria Galietta
Department of Clinical Medicine, University of Milano Bicocca, Monza, Italy
Blood 110:2600-9. 2007..These results identify PSF as a novel NPM/ALK-binding protein and substrate, and suggest that PSF function may be perturbed in NPM/ALK-transformed cells... - hnRNP A1 nucleocytoplasmic shuttling activity is required for normal myelopoiesis and BCR/ABL leukemogenesisAngela Iervolino
Department of Microbiology and Immunology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
Mol Cell Biol 22:2255-66. 2002..Together, these results suggest that the shuttling activity of hnRNP A1 is important for the nucleocytoplasmic trafficking of mRNAs that encode proteins influencing the phenotype of normal and BCR/ABL-transformed myeloid progenitors...
Research Grants
- Role of RNA-Binding Proteins in BCR/ABL LeukemogenesisDanilo Perrotti; Fiscal Year: 2006..3) To determine the BCR/ABL-dependent mechanisms regulating the expression/function of hnRNP K and determine whether hnRNP K function(s) is(are) required for BCR/ABL-induced leukemogenesis. ..
- Role of RNA Binding Proteins in BCR/ABL LeukemogenesisDanilo Perrotti; Fiscal Year: 2009..Thus, it is clear that, if successful, the proposed research will have a strong impact on leukemia research and patient care. ..
- Role of RNA Binding Proteins in BCR/ABL LeukemogenesisDanilo Perrotti; Fiscal Year: 2010..Thus, it is clear that, if successful, the proposed research will have a strong impact on leukemia research and patient care. ..