MANUELA MANCINI

Scopus Publications

AUTOPHAGY INHIBITION POTENTIATES MIDOSTAURIN EFFICACY IN FLT3-MUTATED ACUTE MYELOID LEUKEMIA UNDER HYPOXIC CONDITIONS
Cristina Mosca
Haematologica, 2026
Mutations in FMS-like tyrosine kinase 3 (FLT3) are found in about 30% of newly diagnosed acute myeloid leukemia (AML) patients and confer poor prognosis. Despite the multikinase inhibitor midostaurin (mido) has improved outcomes for FLT3-mutated (FLT3m) AML, relapses occur in over 40% of cases. The hypoxic bone marrow niche provides a protective environment for leukemic stem cells (LSCs), playing a crucial role in the development of resistance mechanisms. We investigated in vitro how hypoxia impacts on the efficacy of mido on FLT3m AML cells and how therapeutic efficacy of mido can be enhanced.Mido and/or chloroquine (Cq) were administered as single agents and in combination to FLT3-ITD AML cell lines MV-4-11 and MOLM-13 under normoxic (20% O2) and hypoxic (1% O2) conditions. Apoptosis induction, cell proliferation, metabolic activity, gene expression changes and protein expression were evaluated after 24 and 48 hours of exposure to the drugs.In FLT3-mutated AML cell lines, the main metabolic alteration due to mido treatment was a reduction in glutamate levels. Gene expression analysis revealed lower transcriptional levels of genes encoding enzymes involved in non-essential amino acid synthesis and m-TORC1 signalling suppression. These results suggests that autophagy was promoted as a potential survival mechanism to evade the antileukemic effects of mido. Co-treatment with the autophagy inhibitor Cq enhanced apoptosis and reduced expression of phosphorylated FLT3 and autophagy-related proteins (BECLIN, ATG3, LC3I-II) under both normoxic and hypoxic conditions. According to autophagy inhibition, the combination reversed Mido-induced mTORC1 suppression and ultimately activated DNA repair pathways, including ATM and p53 signalling.Our data suggest that Cq might contribute to eradicate FLT3m cells in hypoxia. The association of mido with autophagy inhibitors could be evaluated as a therapeutic strategy to overcome LSC resistance in the hypoxic niche.Supported by the AIRC-Fellowship for Italy, Project Code: 26986.
SETD2 LOSS IN CHRONIC MYELOID LEUKEMIA PROMOTES METABOLIC REPROGRAMMING AND GENOMIC INSTABILITY LEADING TO THERAPEUTIC RESISTANCE AND DISEASE PROGRESSION
Manuela Mancini
Haematologica, 2026
Chronic myeloid leukemia (CML) is driven by the Ph chromosome, but additional genetic abnormalities (AGAs) such as ASXL1 mutations and other cytogenetic alterations contribute to poor prognosis and reduced treatment response. SETD2 plays a critical role in DNA repair and chromatin integrity and its non genomic loss-of-function (LOF) has been linked to disease progression in CML. This study examines how SETD2 LOF impacts on CML pathogenesis and its potential as a biomarker for high-risk disease.To investigate the role of SETD2 LOF in CML, cellular models with SETD2 silencing or overexpression were compared using liquid chromatography-tandem mass spectrometry (LC-MS/MS), RNA sequencing (RNA-seq), and chromatin immunoprecipitation sequencing (ChIP-seq). Validation was performed by Western blotting (WB), immunofluorescence (IF), and co-immunoprecipitation (co-IP) in proper cell fractions. Additionally, SNP-array analysis provided genomic insights.Differential transcriptomic profiling revealed SETD2-dependent transcriptional regulation of genes involved in DNA repair (MSH2, MSH6) and metabolic homeostasis (PFKP, LDHA, PDK1) (FIGURE 1A). Differential interactome profiling by LC-MS/MS identified SETD2 interactions with proteins critically involved in mismatch repair (MSH2, MSH6), cell division (α-/β-tubulin), and glycolysis (PFKP, PFKFB3, PD, and LDHA). Notably, SETD2 was also found to interact with key kinases regulating proliferation and stress response, including ERK1/2 and p38 MAPK. Integration of SNP-array analysis after chronic cell exposure to DNA damaging agents with ChIP-seq of SETD2-dependent H3K36me3 deposition sites confirmed that SETD2 plays a direct role in promoting faithful DNA damage response, since breakpoints were enriched at sites where H3K36me3 was disrupted by SETD2 LOF.Notably, we uncovered a novel role for SETD2 LOF in rewiring cellular metabolism: SETD2 re-expression attenuated the glycolytic shift observed in SETD2-deficient cells, as evidenced by downregulation of glycolytic enzymes (FIGURE 1 B, C, D), mitochondrial oxidative phosphorylation and overexpression of IDH1 enzyme which regulates a key step in the TCA, produces NADPH and protects cells from reactive oxygen species, acting as an antioxidant. Finally, SETD2/H3K36me3 deficiency as assessed by WB in total leukocytes could be detected in pts with AGAs at diagnosis and could discriminate pts who subsequently achieved non-optimal vs optimal responses to IM.Our findings point to SETD2 LOF as a key cooperating event in CML, that may act since diagnosis to set the stage for TKI resistance and disease acceleration by:• sustaining BCR::ABL1-independent genomic instability that fuels the acquisition of AGAs• metabolic reprogramming towards glycolysisWhether SETD2 LOF may serve as a biomarker of high-risk disease at diagnosis is an intriguing hypothesis that we are currently exploring in a larger cohort of uniformly treated pts.
Tracking Response and Resistance in Acute Myeloid Leukemia through Single-Cell DNA Sequencing Helps Uncover New Therapeutic Targets
Samantha Bruno, Enrica Borsi, Agnese Patuelli, Lorenza Bandini, Manuela Mancini, Dorian Forte, Jacopo Nanni, Martina Barone, Alessandra Grassi, Gianluca Cristiano, Claudia Venturi, Valentina Robustelli, Giulia Atzeni, Cristina Mosca, Sara De Santis, Cecilia Monaldi, Andrea Poletti, Carolina Terragna, Antonio Curti, Michele Cavo, Simona Soverini, Emanuela Ottaviani
International Journal of Molecular Sciences, 2024
Acute myeloid leukemia (AML) is an aggressive hematologic neoplasia with a complex polyclonal architecture. Among driver lesions, those involving the FLT3 gene represent the most frequent mutations identified at diagnosis. The development of tyrosine kinase inhibitors (TKIs) has improved the clinical outcomes of FLT3-mutated patients (Pt). However, overcoming resistance to these drugs remains a challenge. To unravel the molecular mechanisms underlying therapy resistance and clonal selection, we conducted a longitudinal analysis using a single-cell DNA sequencing approach (MissionBioTapestri® platform, San Francisco, CA, USA) in two patients with FLT3-mutated AML. To this end, samples were collected at the time of diagnosis, during TKI therapy, and at relapse or complete remission. For Pt #1, disease resistance was associated with clonal expansion of minor clones, and 2nd line TKI therapy with gilteritinib provided a proliferative advantage to the clones carrying NRAS and KIT mutations, thereby responsible for relapse. In Pt #2, clonal architecture was less complex, and 1st line TKI therapy with midostaurin was able to eradicate the leukemic clones. Our results corroborate previous findings about clonal selection driven by TKIs, highlighting the importance of a deeper characterization of individual clonal architectures for choosing the best treatment plan for personalized approaches aimed at optimizing outcomes.
SETD2 non genomic loss of function in advanced systemic mastocytosis is mediated by an Aurora kinase A/MDM2 axis and can be therapeutically targeted
Manuela Mancini, Cecilia Monaldi, Sara De Santis, Cristina Papayannidis, Michela Rondoni, Chiara Sartor, Samantha Bruno, Livio Pagano, Marianna Criscuolo, Roberta Zanotti, Massimiliano Bonifacio, Patrizia Tosi, Michel Arock, Peter Valent, Michele Cavo, Simona Soverini
Biomarker Research, 2023
Background The SETD2 tumor suppressor gene encodes a histone methyltransferase that safeguards transcription fidelity and genomic integrity via trimethylation of histone H3 lysine 36 (H3K36Me3). SETD2 loss of function has been observed in solid and hematologic malignancies. We have recently reported that most patients with advanced systemic mastocytosis (AdvSM) and some with indolent or smoldering SM display H3K36Me3 deficiency as a result of a reversible loss of SETD2 due to reduced protein stability. Methods Experiments were conducted in SETD2-proficient (ROSAKIT D816V) and -deficient (HMC-1.2) cell lines and in primary cells from patients with various SM subtypes. A short interfering RNA approach was used to silence SETD2 (in ROSAKIT D816V cells), MDM2 and AURKA (in HMC-1.2 cells). Protein expression and post-translational modifications were assessed by WB and immunoblotting. Protein interactions were tested by using co-immunoprecipitation. Apoptotic cell death was evaluated by flow cytometry after annexin V and propidium iodide staining, respectively. Drug cytotoxicity in in vitro experiments was evaluated by clonogenic assays. Results Here, we show that the proteasome inhibitors suppress cell growth and induce apoptosis in neoplastic mast cells by promoting SETD2/H3K36Me3 re-expression. Moreover, we found that Aurora kinase A and MDM2 are implicated in SETD2 loss of function in AdvSM. In line with this observation, direct or indirect targeting of Aurora kinase A with alisertib or volasertib induced reduction of clonogenic potential and apoptosis in human mast cell lines and primary neoplastic cells from patients with AdvSM. Efficacy of Aurora A or proteasome inhibitors was comparable to that of the KIT inhibitor avapritinib. Moreover, combination of alisertib (Aurora A inhibitor) or bortezomib (proteasome inhibitor) with avapritinib allowed to use lower doses of each drug to achieve comparable cytotoxic effects. Conclusions Our mechanistic insights into SETD2 non-genomic loss of function in AdvSM highlight the potential value of novel therapeutic targets and agents for the treatment of patients who fail or do not tolerate midostaurin or avapritinib.
Prognosis in Chronic Myeloid Leukemia: Baseline Factors, Dynamic Risk Assessment and Novel Insights
Miriam Iezza, Sofia Cortesi, Emanuela Ottaviani, Manuela Mancini, Claudia Venturi, Cecilia Monaldi, Sara De Santis, Nicoletta Testoni, Simona Soverini, Gianantonio Rosti, Michele Cavo, Fausto Castagnetti
Cells, 2023
The introduction of tyrosine kinase inhibitors (TKIs) has changed the treatment paradigm of chronic myeloid leukemia (CML), leading to a dramatic improvement of the outcome of CML patients, who now have a nearly normal life expectancy and, in some selected cases, the possibility of aiming for the more ambitious goal of treatment-free remission (TFR). However, the minority of patients who fail treatment and progress from chronic phase (CP) to accelerated phase (AP) and blast phase (BP) still have a relatively poor prognosis. The identification of predictive elements enabling a prompt recognition of patients at higher risk of progression still remains among the priorities in the field of CML management. Currently, the baseline risk is assessed using simple clinical and hematologic parameters, other than evaluating the presence of additional chromosomal abnormalities (ACAs), especially those at “high-risk”. Beyond the onset, a re-evaluation of the risk status is mandatory, monitoring the response to TKI treatment. Moreover, novel critical insights are emerging into the role of genomic factors, present at diagnosis or evolving on therapy. This review presents the current knowledge regarding prognostic factors in CML and their potential role for an improved risk classification and a subsequent enhancement of therapeutic decisions and disease management.
MPN-182 Droplet Digital PCR for Non-Invasive Detection of the KIT D816V Mutation in the Peripheral Blood of Patients With Suspected Systemic Mastocytosis
Cecilia Monaldi, Sara de Santis, Manuela Mancini, Cristina Papayannidis, Chiara Sartor, Michela Rondoni, Samantha Bruno, Michele Cavo, Simona Soverini
Clinical Lymphoma Myeloma and Leukemia, 2022
CML-184 A Novel Droplet Digital PCR Strategy for Rapid and Sensitive Detection of BCR::ABL1 Kinase Domain Mutations Conferring Resistance to Second-Generation Tyrosine Kinase Inhibitors
Sara de Santis, Cecilia Monaldi, Margherita Martelli, Manuela Mancini, Samantha Bruno, Fausto Castagnetti, Gabriele Gugliotta, Katerina Machova Polakova, Thomas Ernst, Dianna Maar, Adam Corner, Michele Cavo, Simona Soverini
Clinical Lymphoma Myeloma and Leukemia, 2022
Droplet digital PCR for the detection of second-generation tyrosine kinase inhibitor-resistant BCR::ABL1 kinase domain mutations in chronic myeloid leukemia
Simona Soverini, Sara De Santis, Margherita Martelli, Cecilia Monaldi, Fausto Castagnetti, Gabriele Gugliotta, Cristina Papayannidis, Manuela Mancini, Samantha Bruno, Claudia Venturi, Katerina Machova Polakova, Thomas Ernst, Dianna Maar, Adam Corner, Michele Cavo
Leukemia, 2022
Polo-like kinase-1, Aurora kinase A and WEE1 kinase are promising druggable targets in CML cells displaying BCR::ABL1-independent resistance to tyrosine kinase inhibitors
Manuela Mancini, Sara De Santis, Cecilia Monaldi, Fausto Castagnetti, Annalisa Lonetti, Samantha Bruno, Elisa Dan, Barbara Sinigaglia, Gianantonio Rosti, Michele Cavo, Gabriele Gugliotta, Simona Soverini
Frontiers in Oncology, 2022
In chronic myeloid leukemia (CML), Aurora kinase A and Polo like kinase 1 (PLK1), two serine-threonine kinases involved in the maintenance of genomic stability by preserving a functional G2/M checkpoint, have been implicated in BCR::ABL1-independent resistance to the tyrosine kinase inhibitor (TKI) imatinib mesylate and in leukemic stem cell (LSC) persistence. It can be speculated that the observed deregulated activity of Aurora A and Plk1 enhances DNA damage, promoting the occurrence of additional genomic alterations contributing to TKI resistance and ultimately driving progression from chronic phase to blast crisis (BC). In this study, we propose a new therapeutic strategy based on the combination of Aurora kinase A or PLK1 inhibition with danusertib or volasertib, respectively, and WEE1 inhibition with AZD1775. Danusertib and volasertib used as single drugs induced apoptosis and G2/M-phase arrest, associated with accumulation of phospho-WEE1. Subsequent addition of the WEE1 inhibitor AZD1775 in combination significantly enhanced the induction of apoptotic cell death in TKI-sensitive and -resistant cell lines as compared to both danusertib and volasertib alone and to the simultaneous combination. This schedule indeed induced a significant increase of the DNA double-strand break marker γH2AX, forcing the cells through successive replication cycles ultimately resulting in apoptosis. Finally, combination of danusertib or volasertib+AZD1775 significantly reduced the clonogenic potential of CD34+ CML progenitors from BC patients. Our results may have implications for the development of innovative therapeutic approaches aimed to improve the outcomes of patients with multi-TKI-resistant or BC CML.
Combined Inhibition of Polo-like Kinase-1 and Wee1 as a New Therapeutic Strategy to Induce Apoptotic Cell Death in Neoplastic Mast Cells
Manuela Mancini, Cecilia Monaldi, Sara De Santis, Michela Rondoni, Cristina Papayannidis, Chiara Sartor, Antonio Curti, Samantha Bruno, Michele Cavo, Simona Soverini
Cancers, 2022
Systemic mastocytosis (SM) is due to the pathologic accumulation of neoplastic mast cells in one or more extracutaneous organ(s). Although midostaurin, a multikinase inhibitor active against both wild-type and D816V-mutated KIT, improves organ damage and symptoms, a proportion of patients relapse or have resistant disease. It is well known that Aurora kinase A (AKA) over-expression promotes tumorigenesis, but its role in the pathogenesis of systemic mastocytosis (SM) has not yet been investigated. Evidence from the literature suggests that AKA may confer cancer cell chemo-resistance, inhibit p53, and enhance Polo-like kinase 1 (Plk1), CDK1, and cyclin B1 to promote cell cycle progression. In this study, we aimed to investigate the pathogenetic role of AKA and Plk1 in the advanced forms of SM. We demonstrate here, for the first time, that SM cell lines display hyper-phosphorylated AKA and Plk1. Danusertib (Aurora kinase inhibitor) and volasertib (Plk1 inhibitor) inhibited growth and induced apoptotic cell death in HMC-1.1 and -1.2 cells. Their growth-inhibitory effects were associated with cell cycle arrest and the activation of apoptosis. Cell cycle arrest was associated with increased levels of phospho-Wee1. Wee1 inhibition by MK1775 after 24 h treatment with danusertib or volasertib, when cells were arrested in G2 phase and Wee1, was overexpressed and hyper-activated, resulting in a significantly higher rate of apoptosis than that obtained from concomitant treatment with danusertib or volasertib + MK1775 for 48 h. In conclusion, Plk1 and AKA, alone or together with Wee1, are attractive therapeutic targets in neoplastic MCs. Repurposing Plk1 or AKA ± Wee1 inhibitors in advanced clinical development for other indications is a therapeutic strategy worthy of being explored, in order to improve the outcome of patients with advanced SM.
Overcoming Resistance to Kinase Inhibitors: The Paradigm of Chronic Myeloid Leukemia
Sara De Santis, Cecilia Monaldi, Manuela Mancini, Samantha Bruno, Michele Cavo, Simona Soverini
Oncotargets and Therapy, 2022
Case Report: A Novel Activating FLT3 Mutation in Acute Myeloid Leukemia
Samantha Bruno, Lorenza Bandini, Agnese Patuelli, Valentina Robustelli, Claudia Venturi, Manuela Mancini, Dorian Forte, Sara De Santis, Cecilia Monaldi, Alessandra Grassi, Gabriella Chiurumbolo, Stefania Paolini, Gianluca Cristiano, Cristina Papayannidis, Chiara Sartor, Jacopo Nanni, Emanuela Ottaviani, Antonio Curti, Michele Cavo, Simona Soverini
Frontiers in Oncology, 2021
Targeting leukemic stem cells in chronic myeloid leukemia: Is it worth the effort?
Simona Soverini, Sara De Santis, Cecilia Monaldi, Samantha Bruno, Manuela Mancini
International Journal of Molecular Sciences, 2021
The role of hypoxic bone marrow microenvironment in acute myeloid leukemia and future therapeutic opportunities
Samantha Bruno, Manuela Mancini, Sara De Santis, Cecilia Monaldi, Michele Cavo, Simona Soverini
International Journal of Molecular Sciences, 2021
Systemic mastocytosis: Molecular landscape and implications for treatment
Cecilia Monaldi, Sara De Santis, Manuela Mancini, Samantha Bruno, Michele Cavo, Simona Soverini
Mediterranean Journal of Hematology and Infectious Diseases, 2021
Recent advances in the molecular biology of systemic mastocytosis: Implications for diagnosis, prognosis, and therapy
Margherita Martelli, Cecilia Monaldi, Sara De Santis, Samantha Bruno, Manuela Mancini, Michele Cavo, Simona Soverini
International Journal of Molecular Sciences, 2020
Ponatinib treatment in chronic myeloid leukemia cell lines targets aurora kinase A/FOXM1 axis
Manuela Mancini, Sara De Santis, Cecilia Monaldi, Luana Bavaro, Margherita Martelli, Gabriele Gugliotta, Fausto Castagnetti, Gianantonio Rosti, Maria Alessandra Santucci, Giovanni Martinelli, Michele Cavo, Simona Soverini
Hematological Oncology, 2020
Hyper-activation of Aurora kinase a-polo-like kinase 1-FOXM1 axis promotes chronic myeloid leukemia resistance to tyrosine kinase inhibitors
M. Mancini, S. De Santis, C. Monaldi, L. Bavaro, M. Martelli, F. Castagnetti, G. Gugliotta, G. Rosti, M. A. Santucci, G. Martinelli, M. Cavo, S. Soverini
Journal of Experimental and Clinical Cancer Research, 2019
Chronic myeloid leukemia: The paradigm of targeting oncogenic tyrosine kinase signaling and counteracting resistance for successful cancer therapy
Simona Soverini, Manuela Mancini, Luana Bavaro, Michele Cavo, Giovanni Martinelli
Molecular Cancer, 2018
SETD2 and histone H3 lysine 36 methylation deficiency in advanced systemic mastocytosis
G Martinelli, M Mancini, C De Benedittis, M Rondoni, C Papayannidis, M Manfrini, M Meggendorfer, R Calogero, V Guadagnuolo, M C Fontana, L Bavaro, A Padella, E Zago, L Pagano, R Zanotti, L Scaffidi, G Specchia, F Albano, S Merante, C Elena, P Savini, D Gangemi, P Tosi, F Ciceri, G Poletti, L Riccioni, F Morigi, M Delledonne, T Haferlach, M Cavo, P Valent, S Soverini
Leukemia, 2018
FOXM1 Transcription Factor: A New Component of Chronic Myeloid Leukemia Stem Cell Proliferation Advantage
Manuela Mancini, Fausto Castagnetti, Simona Soverini, Elisa Leo, Caterina De Benedittis, Gabriele Gugliotta, Gianantonio Rosti, Luana Bavaro, Sara De Santis, Cecilia Monaldi, Margherita Martelli, Maria Alessandra Santucci, Michele Cavo, Giovanni Martinelli
Journal of Cellular Biochemistry, 2017
CML HSCs: Are the true enemies for the patient?
Manuela Mancini
Current Drug Targets, 2017
Chibby 1: A new component of β-catenin-signaling in chronic myeloid leukemia
Manuela Mancini, Simona Soverini, Gabriele Gugliotta, Maria Alessandra Santucci, Gianantonio Rosti, Michele Cavo, Giovanni Martinelli, Fausto Castagnetti
Oncotarget, 2017
In chronic myeloid leukemia patients on second-line tyrosine kinase inhibitor therapy, deep sequencing of BCR-ABL1 at the time of warning may allow sensitive detection of emerging drug-resistant mutants
Simona Soverini, Caterina De Benedittis, Fausto Castagnetti, Gabriele Gugliotta, Manuela Mancini, Luana Bavaro, Katerina Machova Polakova, Jana Linhartova, Alessandra Iurlo, Domenico Russo, Fabrizio Pane, Giuseppe Saglio, Gianantonio Rosti, Michele Cavo, Michele Baccarani, Giovanni Martinelli
BMC Cancer, 2016
Clinical impact of low-burden BCR-ABL1 mutations detectable by amplicon deep sequencing in Philadelphia-positive acute lymphoblastic leukemia patients
S Soverini, C De Benedittis, C Papayannidis, K Machova Polakova, C Venturi, D Russo, P Bresciani, A Iurlo, M Mancini, A Vitale, S Chiaretti, R Foà, E Abruzzese, F Sorà, A Kohlmann, T Haferlach, M Baccarani, M Cavo, G Martinelli
Leukemia, 2016
Present and future of molecular monitoring in chronic myeloid leukaemia
Simona Soverini, Caterina De Benedittis, Manuela Mancini, Giovanni Martinelli
British Journal of Haematology, 2016
Next-generation sequencing for sensitive detection of BCR-ABL1 mutations relevant to tyrosine kinase inhibitor choice in imatinib-resistant patients
Simona Soverini, Caterina De Benedittis, Katerina Machova Polakova, Jana Linhartova, Fausto Castagnetti, Gabriele Gugliotta, Cristina Papayannidis, Manuela Mancini, Hana Klamova, Marzia Salvucci, Monica Crugnola, Alessandra Iurlo, Francesco Albano, Domenico Russo, Gianantonio Rosti, Michele Cavo, Michele Baccarani, Giovanni Martinelli
Oncotarget, 2016
Best practices in chronic myeloid leukemia monitoring and management
Simona Soverini, Caterina De Benedittis, Manuela Mancini, Giovanni Martinelli
Oncologist, 2016
14-3-3 binding and SUMOylation concur to the down-modulation of β-catenin antagonist Chibby 1 in chronic myeloid leukemia
Manuela Mancini, Elisa Leo, Ken-Ichi Takemaru, Virginia Campi, Fausto Castagnetti, Simona Soverini, Caterina De Benedittis, Gianantonio Rosti, Michele Cavo, Maria Alessandra Santucci, Giovanni Martinelli
Plos One, 2015
Mutations in the BCR-ABL1 Kinase Domain and Elsewhere in Chronic Myeloid Leukemia
Simona Soverini, Caterina de Benedittis, Manuela Mancini, Giovanni Martinelli
Clinical Lymphoma Myeloma and Leukemia, 2015
DNA Methyltransferase 1 Drives Transcriptional Down-Modulation of β Catenin Antagonist Chibby1 Associated with the BCR-ABL1 Gene of Chronic Myeloid Leukemia
Elisa Leo, Manuela Mancini, Fausto Castagnetti, Gabriele Gugliotta, Maria Alessandra Santucci, Giovanni Martinelli
Journal of Cellular Biochemistry, 2015
A calpain-cleaved fragment of β-catenin promotes BCRABL1+ cell survival evoked by autophagy induction in response to imatinib
Manuela Mancini, Elisa Leo, Virginia Campi, Fausto Castagnetti, Luca Zazzeroni, Gabriele Gugliotta, Maria Alessandra Santucci, Giovanni Martinelli
Cellular Signalling, 2014
Platelet-derived growth factor alpha mediates the proliferation of peripheral T-cell lymphoma cells via an autocrine regulatory pathway
P P Piccaluga, M Rossi, C Agostinelli, F Ricci, A Gazzola, S Righi, F Fuligni, M A Laginestra, M Mancini, M R Sapienza, A De Renzo, P L Tazzari, D Gibellini, P Went, F Alviano, P L Zinzani, G P Bagnara, G Inghirami, C Tripodo, S A Pileri, on behalf of the AIRC 5xMille consortium ‘Genetics-driven targeted management of lymphoid malignancies’, the European T-cell Lymphoma Study Group
Leukemia, 2014
Molecular profiling of blastic plasmacytoid dendritic cell neoplasm reveals a unique pattern and suggests selective sensitivity to NF-kB pathway inhibition
M R Sapienza, F Fuligni, C Agostinelli, C Tripodo, S Righi, M A Laginestra, A Pileri, M Mancini, M Rossi, F Ricci, A Gazzola, F Melle, C Mannu, F Ulbar, M Arpinati, M Paulli, T Maeda, D Gibellini, L Pagano, N Pimpinelli, M Santucci, L Cerroni, C M Croce, F Facchetti, P P Piccaluga, S A Pileri, for the AIRC 5xMille consortium ‘Genetics-driven targeted management of lymphoid malignancies’, the Italian Registry on Blastic Plasmacytoid Dendritic Cell Neoplasm
Leukemia, 2014
BCR-ABL1-associated reduction of beta catenin antagonist Chibby1 in chronic myeloid leukemia
Elisa Leo, Manuela Mancini, Michela Aluigi, Simona Luatti, Fausto Castagnetti, Nicoletta Testoni, Simona Soverini, Maria Alessandra Santucci, Giovanni Martinelli
Plos One, 2013
Chibby drives β catenin cytoplasmic accumulation leading to activation of the unfolded protein response in BCR-ABL1+ cells
Manuela Mancini, Elisa Leo, Ken-Ichi Takemaru, Virginia Campi, Enrica Borsi, Fausto Castagnetti, Gabriele Gugliotta, Maria Alessandra Santucci, Giovanni Martinelli
Cellular Signalling, 2013
DNA hypermethylation promotes the low expression of pro-apoptotic BCL2L11 associated with BCR-ABL1 fusion gene of chronic myeloid leukaemia
Elisa Leo, Manuela Mancini, Michela Aluigi, Fausto Castagnetti, Giovanni Martinelli, Enza Barbieri, Maria A. Santucci
British Journal of Haematology, 2012
Gadd45a transcriptional induction elicited by the Aurora kinase inhibitor MK-0457 in Bcr-Abl-expressing cells is driven by Oct-1 transcription factor
Manuela Mancini, Elisa Leo, Michela Aluigi, Chiara Marcozzi, Enrica Borsi, Enza Barbieri, Maria Alessandra Santucci
Leukemia Research, 2012
Cytoplasmatic compartmentalization by Bcr-Abl promotes TET2 loss-of-function in chronic myeloid leukemia
Manuela Mancini, Nevena Veljkovic, Elisa Leo, Michela Aluigi, Enrica Borsi, Chiara Galloni, Ilaria Iacobucci, Enza Barbieri, Maria Alessandra Santucci
Journal of Cellular Biochemistry, 2012
Histone H3 covalent modifications driving response of BCR-ABL1+ cells sensitive and resistant to imatinib to Aurora kinase inhibitor MK-0457
Manuela Mancini, Michela Aluigi, Elisa Leo, Chiara Marcozzi, Fausto Castagnetti, Enza Barbieri, Maria Alessandra Santucci
British Journal of Haematology, 2012
Computational techniques are valuable tools for the discovery of protein-protein interaction inhibitors: The 14-3-3σ case
Valentina Corradi, Manuela Mancini, Maria Alessandra Santucci, Teresa Carlomagno, Domenico Sanfelice, Mattia Mori, Giulia Vignaroli, Federico Falchi, Fabrizio Manetti, Marco Radi, Maurizio Botta
Bioorganic and Medicinal Chemistry Letters, 2011
Multiple phosphorylation sites at the C-terminus regulate nuclear import of HCMV DNA polymerase processivity factor ppUL44
Gualtiero Alvisi, Oriano Marin, Gregory Pari, Manuela Mancini, Simone Avanzi, Arianna Loregian, David A. Jans, Alessandro Ripalti
Virology, 2011
A new nonpeptidic inhibitor of 14-3-3 induces apoptotic cell death in chronic myeloid leukemia sensitive or resistant to imatinib
Manuela Mancini, Valentina Corradi, Sara Petta, Enza Barbieri, Fabrizio Manetti, Maurizio Botta, Maria Alessandra Santucci
Journal of Pharmacology and Experimental Therapeutics, 2011
New SRC/ABL inhibitors for chronic myeloid leukemia therapy show selectivity for T315I ABL mutant CD34+ cells
Maria Alessandra Santucci, Manuela Mancini, Valentina Corradi, Ilaria lacobucci, Giovanni Martinelli, Maurizio Botta, Silvia Schenone
Investigational New Drugs, 2010
Characterization of a new monoclonal antibody against PAX5/BASP in 1525 paraffin-embedded human and animal tissue samples
Claudio Agostinelli, Elena Sabattini, Jakob Oemar Gjørret, Simona Righi, Maura Rossi, Manuela Mancini, Pier Paolo Piccaluga, Francesco Bacci, Teresa Marafioti, Giuliano Bettini, Brunangelo Falini, Stefano A. Pileri
Applied Immunohistochemistry and Molecular Morphology, 2010
Identification of the first non-peptidic small molecule inhibitor of the c-Abl/14-3-3 protein-protein interactions able to drive sensitive and Imatinib-resistant leukemia cells to apoptosis
Valentina Corradi, Manuela Mancini, Fabrizio Manetti, Sara Petta, Maria Alessandra Santucci, Maurizio Botta
Bioorganic and Medicinal Chemistry Letters, 2010
Zinc-finger transcription factor slug contributes to the survival advantage of chronic myeloid leukemia cells
Manuela Mancini, Sara Petta, Ilaria Iacobucci, Valentina Salvestrini, Enza Barbieri, Maria Alessandra Santucci
Cellular Signalling, 2010
MTOR inhibitor RAD001 (Everolimus) enhances the effects of imatinib in chronic myeloid leukemia by raising the nuclear expression of c-ABL protein
Manuela Mancini, Valentina Corradi, Sara Petta, Giovanni Martinelli, Enza Barbieri, Maria Alessandra Santucci
Leukemia Research, 2010
RAD 001 (everolimus) prevents mTOR and Akt late re-activation in response to imatinib in chronic myeloid leukemia
Manuela Mancini, Sara Petta, Giovanni Martinelli, Enza Barbieri, Maria A. Santucci
Journal of Cellular Biochemistry, 2010
14-3-3 ligand prevents nuclear import of c-ABL protein in chronic myeloid leukemia
Manuela Mancini, Nevena Veljkovic, Valentina Corradi, Elisa Zuffa, Patrizia Corrado, Eleonora Pagnotta, Giovanni Martinelli, Enza Barbieri, Maria Alessandra Santucci
Traffic, 2009
C6-unsubstituted pyrazolo[3,4-d]pyrimidines are dual Src/ Abl inhibitors effective against imatinib mesylate resistant chronic myeloid leukemia cell lines
Maria Alessandra Santucci, Valentina Corradi, Manuela Mancini, Fabrizio Manetti, Marco Radi, Silvia Schenone, Maurizio Botta
Chemmedchem, 2009
Acetylation of FOXO3a transcription factor in response to imatinib of chronic myeloid leukemia
P Corrado, M Mancini, G Brusa, S Petta, G Martinelli, E Barbieri, M A Santucci
Leukemia, 2009
P53 oncosuppressor influences selection of genomic imbalances in response to ionizing radiations in human osteosarcoma cell line SAOS-2
Elisa Zuffa, Manuela Mancini, Gianluca Brusa, Eleonora Pagnotta, Claudia Maria Hattinger, Massimo Serra, Daniel Remondini, Gastone Castellani, Patrizia Corrado, Enza Barbieri, Maria Alessandra Santucci
International Journal of Radiation Biology, 2008
Discovery and SAR of 1,3,4-thiadiazole derivatives as potent Abl tyrosine kinase inhibitors and cytodifferentiating agents
Marco Radi, Emmanuele Crespan, Giorgia Botta, Federico Falchi, Giovanni Maga, Fabrizio Manetti, Valentina Corradi, Manuela Mancini, Maria Alessandra Santucci, Silvia Schenone, Maurizio Botta
Bioorganic and Medicinal Chemistry Letters, 2008
Retraction:IPO-trimethylation of histone H3-lysine9 associated with P210 BCR-ABL tyrosine kinase of chronic myeloid leukaemia
Manuela Mancini, Elisa Zuffa, Nevena Veljkovic, Gianluca Brusa, Patrizia Corrado, Valentina Corradi, Giovanni Martinelli, Enza Barbieri, Maria Alessandra Santucci
British Journal of Haematology, 2008
Persistent Cdk2 inactivation drives growth arrest of BCR-ABL-expressing cells in response to dual inhibitor of SRC and ABL kinases SKI606
Manuela Mancini, Gianluca Brusa, Elisa Zuffa, Patrizia Corrado, Giovanni Martinelli, Tiziana Grafone, Enza Barbieri, Maria Alessandra Santucci
Leukemia Research, 2007
Genomic imbalances associated with secondary acute leukemias in Hodgkin lymphoma
Gianluca Brusa, Elisa Zuffa, Claudia Hattinger, Massimo Serra, Daniel Remondini, Gastone Castellani, Simona Righi, Cristina Campidelli, Stefano Pileri, Pier Zinzani, Annalisa Gabriele, Manuela Mancini, Patrizia Corrado, Enza Barbieri, Maria Santucci
Oncology Reports, 2007
Retraction:P210 Bcr-abl tyrosine kinase interaction with histone deacetylase 1 modifies histone H4 acetylation and chromatin structure of chronic myeloid leukaemia haematopoietic progenitors
Gianluca Brusa, Elisa Zuffa, Manuela Mancini, Michela Benvenuti, Natalia Calonghi, Enza Barbieri, Maria Alessandra Santucci
British Journal of Haematology, 2006
Tyrosine kinase inhibitor STI571 (Imatinib) cooperates with wild-type p53 on K562 cell line to enhance its proapoptotic effects
Gianluca Brusa, Manuela Mancini, Fabio Campanini, Alberto Calabrò, Elisa Zuffa, Enza Barbieri, Maria Alessandra Santucci
Acta Haematologica, 2005
Ectopic expression of p210 bcr-abl tyrosine kinase in chronic myeloid leukaemia downregulates DR4 receptor expression
European Journal of Oncology, 2005
Chk2 drives late G1/early S phase arrest of clonal myeloid progenitors expressing the p210 BCR-ABL tyrosine kinase in response to STI571
Lucia Mazzacurati, Laura Pattacini, Gianluca Brusa, Manuela Mancini, Michela Benvenuti, Enza Barbieri, Giovanni Martinelli, Michele Baccarani, Joel S Greenberger, Maria Alessandra Santucci
Hematology Journal, 2004
Endoplasmic reticulum stress initiates apoptotic death induced by STI571 inhibition of p210 bcr-abl tyrosine kinase
Laura Pattacini, Manuela Mancini, Lucia Mazzacurati, Gianluca Brusa, Michela Benvenuti, Giovanni Martinelli, Michele Baccarani, Maria Alessandra Santucci
Leukemia Research, 2004
The p210BCR-ABL tyrosine kinase of chronic myeloid leukemia causes resistance to radio-induced apoptotic death by inhibiting the proapoptotic BAX gene [8]
M Mancini, G Brusa, M Benvenuti, L Mazzacurati, F Campanini, E Barbieri, S Cammelli, N Calonghi, G Martinelli, M Baccarani, M A Santucci
Leukemia, 2004
p53 loss of function enhances genomic instability and accelerates clonal evolution of murine myeloid progenitors expressing the p210BCR-ABL tyrosine kinase
Haematologica, 2003

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