Danilo Perrotti

article

Precision immunotherapy, mutational landscape, and emerging tools to optimize clinical outcomes in patients with classical myeloproliferative neoplasms

Tariq I. Mughal, Thomas Lion, Omar Abdel‐Wahab, Ruben Mesa, more

Hematological Oncology > 36 > 5 > 740 - 748

Following the 47th American Society of Hematology Meeting in 2005, the late John Goldman and Tariq Mughal commenced a conference, the 1st Post‐ASH Workshop, which brought together clinicians and scientists, to accelerate the adoption of new therapies for patients with myeloproliferative neoplasms (MPNs). The concept began with recognition of the CML success story following imatinib therapy, the discovery...

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Downregulation of p53-inducible microRNAs 192, 194, and 215 Impairs the p53/MDM2 Autoregulatory Loop in Multiple Myeloma Development

Flavia Pichiorri, Sung-Suk Suh, Alberto Rocci, Luciana De Luca, more

Cancer Cell > 2016 > 30 > 2 > 349-351

article

Protein phosphatase 2A: a target for anticancer therapy

Danilo Perrotti, Paolo Neviani

The Lancet Oncology > 2013 > 14 > 6 > e229-e238

Protein phosphatase 2A (PP2A), one of the main serine–threonine phosphatases in mammalian cells, maintains cell homoeostasis by counteracting most of the kinase-driven intracellular signalling pathways. Unrestrained activation of oncogenic kinases together with inhibition of tumour suppressors is often required for development of cancer. PP2A has been shown to be genetically altered or functionally...

article

Aberrant Overexpression of IL-15 Initiates Large Granular Lymphocyte Leukemia through Chromosomal Instability and DNA Hypermethylation

Anjali Mishra, Shujun Liu, Gregory H. Sams, Douglas P. Curphey, more

Cancer Cell > 2012 > 22 > 5 > 645-655

How inflammation causes cancer is unclear. Interleukin-15 (IL-15) is a pro-inflammatory cytokine elevated in human large granular lymphocyte (LGL) leukemia. Mice overexpressing IL-15 develop LGL leukemia. Here, we show that prolonged in vitro exposure of wild-type (WT) LGL to IL-15 results in Myc-mediated upregulation of aurora kinases, centrosome aberrancies, and aneuploidy. Simultaneously, IL-15...

article

Downregulation of p53-inducible microRNAs 192, 194, and 215 Impairs the p53/MDM2 Autoregulatory Loop in Multiple Myeloma Development

Flavia Pichiorri, Sung-Suk Suh, Alberto Rocci, Luciana De Luca, more

Cancer Cell > 2010 > 18 > 4 > 367-381

In multiple myeloma (MM), an incurable B cell neoplasm, mutation or deletion of p53 is rarely detected at diagnosis. Using small-molecule inhibitors of MDM2, we provide evidence that miR-192, 194, and 215, which are downregulated in a subset of newly diagnosed MMs, can be transcriptionally activated by p53 and then modulate MDM2 expression. Furthermore, ectopic re-expression of these miRNAs in MM...

article

Wnt/Ca2+/NFAT Signaling Maintains Survival of Ph+ Leukemia Cells upon Inhibition of Bcr-Abl

Mark A. Gregory, Tzu L. Phang, Paolo Neviani, Francesca Alvarez-Calderon, more

Cancer Cell > 2010 > 18 > 1 > 74-87

Although Bcr-Abl kinase inhibitors have proven effective in the treatment of chronic myeloid leukemia (CML), they generally fail to eradicate Bcr-Abl ⁺ leukemia cells. To identify genes whose inhibition sensitizes Bcr-Abl ⁺ leukemias to killing by Bcr-Abl inhibitors, we performed an RNAi-based synthetic lethal screen with imatinib mesylate in CML cells. This screen identified numerous...

article

Sp1/NFκB/HDAC/miR-29b Regulatory Network in KIT-Driven Myeloid Leukemia

Shujun Liu, Lai-Chu Wu, Jiuxia Pang, Ramasamy Santhanam, more

Cancer Cell > 2010 > 17 > 4 > 333-347

The biologic and clinical significance of KIT overexpression that associates with KIT gain-of-function mutations occurring in subsets of acute myeloid leukemia (AML) (i.e., core binding factor AML) is unknown. Here, we show that KIT mutations lead to MYC-dependent miR-29b repression and increased levels of the miR-29b target Sp1 in KIT-driven leukemia. Sp1 enhances its own expression by participating...

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miR-328 Functions as an RNA Decoy to Modulate hnRNP E2 Regulation of mRNA Translation in Leukemic Blasts

Anna M. Eiring, Jason G. Harb, Paolo Neviani, Christopher Garton, more

Cell > 2010 > 140 > 5 > 652-665

MicroRNAs and heterogeneous ribonucleoproteins (hnRNPs) are posttranscriptional gene regulators that bind mRNA in a sequence-specific manner. Here, we report that loss of miR-328 occurs in blast crisis chronic myelogenous leukemia (CML-BC) in a BCR/ABL dose- and kinase-dependent manner through the MAPK-hnRNP E2 pathway. Restoration of miR-328 expression rescues differentiation and impairs survival...

article

Protein phosphatase 2A (PP2A), a drugable tumor suppressor in Ph1(+) leukemias

Danilo Perrotti, Paolo Neviani

Cancer and Metastasis Reviews > 2008 > 27 > 2 > 159-168

Protein phosphatase-2A (PP2A) is one of the major cellular serine-threonine phosphatases and is involved in the regulation of cell homeostasis through the negative regulation of signaling pathways initiated by protein kinases. As several cancers are characterized by the aberrant activity of oncogenic kinases, it was not surprising that a phosphatase like PP2A has progressively been considered as a...

article

Rac Guanosine Triphosphatases Represent Integrating Molecular Therapeutic Targets for BCR-ABL-Induced Myeloproliferative Disease

Emily K. Thomas, Jose A. Cancelas, Hee-Don Chae, Adrienne D. Cox, more

Cancer Cell > 2007 > 12 > 5 > 467-478

Chronic myelogenous leukemia (CML) is a clonal myeloproliferative disease (MPD) initiated by expression of the p210-BCR-ABL fusion protein. We demonstrate in a murine model of p210-BCR-ABL-induced MPD that gene targeting of Rac1 and Rac2 significantly delays or abrogates disease development. Attenuation of the disease phenotype is associated with severely diminished p210-BCR-ABL-induced downstream...

article

Corrigendum to “Efficient delivery of a Bcl2-specific antisense oligodeoxyribonucleotide (G3139) via transferrin receptor targeted liposomes” [Journal of Controlled Release 112 (2006) 199–207]

Shih-Jiuan Chiu, Shujun Liu, Danilo Perrotti, Guido Marcucci, more

Journal of Controlled Release > 2006 > 114 > 1 > 126-127

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Efficient delivery of a Bcl-2-specific antisense oligodeoxyribonucleotide (G3139) via transferrin receptor-targeted liposomes

Shih-Jiuan Chiu, Shujun Liu, Danilo Perrotti, Guido Marcucci, more

Journal of Controlled Release > 2006 > 112 > 2 > 199-207

A novel transferrin receptor (TfR)-targeted liposomal formulation was synthesized and evaluated for the delivery of a phosphorothioate antisense oligodeoxyribonucleotide (ODN) (G3139, oblimerson sodium, or Genasense™) to Bcl-2 in K562 leukemia cells. Liposomes composed of DC-Chol/egg PC/PEG–DSPE (25:73.5:1.5, mol/mol/mol) were loaded with G3139 with high efficiency (70–80%). To prepare targeted liposomes,...

article

The tumor suppressor PP2A is functionally inactivated in blast crisis CML through the inhibitory activity of the BCR/ABL-regulated SET protein

Paolo Neviani, Ramasamy Santhanam, Rossana Trotta, Mario Notari, more

Cancer Cell > 2005 > 8 > 5 > 355-368

The oncogenic BCR/ABL kinase activity induces and maintains chronic myelogenous leukemia (CML). We show here that, in BCR/ABL-transformed cells and CML blast crisis (CML-BC) progenitors, the phosphatase activity of the tumor suppressor PP2A is inhibited by the BCR/ABL-induced expression of the PP2A inhibitor SET. In imatinib-sensitive and -resistant (T315I included) BCR/ABL ⁺ cell lines and...

article

BCR/ABL activates mdm2 mRNA translation via the La antigen

Rossana Trotta, Tatiana Vignudelli, Olivia Candini, Robert V. Intine, more

Cancer Cell > 2003 > 3 > 2 > 145-160

In a BCR/ABL-expressing myeloid precursor cell line, p53 levels were markedly downmodulated. Expression of MDM2, the negative regulator of p53, was upregulated in a tyrosine kinase-dependent manner in growth factor-independent BCR/ABL-expressing cells, and in accelerated phase and blast crisis CML samples. Increased MDM2 expression was associated with enhanced mdm2 mRNA translation, which required...

article

The Nucleoside Diphosphate Kinase Activity of DRnm23 Is Not Required for Inhibition of Differentiation and Induction of Apoptosis in 32Dcl3 Myeloid Precursor Cells

Donatella Venturelli, Vincenzo Cesi, Stephane Ransac, Andrew Engelhard, more

Experimental Cell Research > 2000 > 257 > 2 > 265-271

DRnm23 belongs to a multigene family which includes nm23-H1, the first bona fide metastasis suppressor gene, nm23-H2, nm23-H4, and nm23-H5. Like nm23-H1, nm23-H2, and nm23-H4, DRnm23 possesses nucleoside diphosphate kinase (NDPK) activity. Upon overexpression in myeloid precursor 32Dcl3 cells, DRnm23 inhibits granulocytic differentiation and promotes apoptosis. Two specific mutants of DRnm23 (H134Q...

article

The Interferon Regulatory Factors 1 and 2 Bind to a Segment of the Human c-myb First Intron: Possible Role in the Regulation of c-myb Expression

Livia Manzella, Rossana Gualdi, Danilo Perrotti, Nicholas C. Nicolaides, more

Experimental Cell Research > 2000 > 256 > 1 > 248-256

The preferential expression of the protooncogene c-myb in hematopoietic cells is in part regulated by a mechanism of transcriptional block in the first intron. By electrophoresis mobility shift assays using probes corresponding to different segments of the putative human c-myb intron 1 transcription pause region and nuclear extracts from myeloid leukemia HL 60 and fibroblast WI 38 cells, we detected...

article

Structure and Growth-Dependent Regulation of the Human Cyclin B1 Promoter

Giulia Piaggio, Andrea Farina, Danilo Perrotti, Isabella Manni, more

Experimental Cell Research > 1995 > 216 > 2 > 396-402

As a step toward defining the signals important for the regulation of cyclin B1 expression, we cloned, sequenced, and partially characterized a 1012-bp genomic fragment encompassing the human cyclin B1 promoter. By transient expression experiments, we found that promoter activity resides within a -150/+182-bp DNA fragment. The activity of this promoter fragment was high in asynchronous NIH-3T3 cells,...

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Search results for: Danilo Perrotti

Precision immunotherapy, mutational landscape, and emerging tools to optimize clinical outcomes in patients with classical myeloproliferative neoplasms

Downregulation of p53-inducible microRNAs 192, 194, and 215 Impairs the p53/MDM2 Autoregulatory Loop in Multiple Myeloma Development

Protein phosphatase 2A: a target for anticancer therapy

Aberrant Overexpression of IL-15 Initiates Large Granular Lymphocyte Leukemia through Chromosomal Instability and DNA Hypermethylation

Downregulation of p53-inducible microRNAs 192, 194, and 215 Impairs the p53/MDM2 Autoregulatory Loop in Multiple Myeloma Development

Wnt/Ca2+/NFAT Signaling Maintains Survival of Ph+ Leukemia Cells upon Inhibition of Bcr-Abl

Sp1/NFκB/HDAC/miR-29b Regulatory Network in KIT-Driven Myeloid Leukemia

miR-328 Functions as an RNA Decoy to Modulate hnRNP E2 Regulation of mRNA Translation in Leukemic Blasts

Protein phosphatase 2A (PP2A), a drugable tumor suppressor in Ph1(+) leukemias

Rac Guanosine Triphosphatases Represent Integrating Molecular Therapeutic Targets for BCR-ABL-Induced Myeloproliferative Disease

Corrigendum to “Efficient delivery of a Bcl2-specific antisense oligodeoxyribonucleotide (G3139) via transferrin receptor targeted liposomes” [Journal of Controlled Release 112 (2006) 199–207]

Efficient delivery of a Bcl-2-specific antisense oligodeoxyribonucleotide (G3139) via transferrin receptor-targeted liposomes

The tumor suppressor PP2A is functionally inactivated in blast crisis CML through the inhibitory activity of the BCR/ABL-regulated SET protein

BCR/ABL activates mdm2 mRNA translation via the La antigen

The Nucleoside Diphosphate Kinase Activity of DRnm23 Is Not Required for Inhibition of Differentiation and Induction of Apoptosis in 32Dcl3 Myeloid Precursor Cells

The Interferon Regulatory Factors 1 and 2 Bind to a Segment of the Human c-myb First Intron: Possible Role in the Regulation of c-myb Expression

Structure and Growth-Dependent Regulation of the Human Cyclin B1 Promoter

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