A5048891781- Chronic Myeloid Leukemia Treatments
- Chronic Lymphocytic Leukemia Research
- Acute Myeloid Leukemia Research
- Lung Cancer Treatments and Mutations
- Eosinophilic Disorders and Syndromes
- Lymphoma Diagnosis and Treatment
- Cancer Genomics and Diagnostics
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Immune Cell Function and Interaction
- Cancer therapeutics and mechanisms
- Epigenetics and DNA Methylation
- Cardiac Valve Diseases and Treatments
- SARS-CoV-2 and COVID-19 Research
- Lung Cancer Research Studies
- Genomics and Rare Diseases
- Acute Lymphoblastic Leukemia research
- RNA modifications and cancer
- Cardiovascular Function and Risk Factors
- CAR-T cell therapy research
- Immunodeficiency and Autoimmune Disorders
- Evolution and Genetic Dynamics
- Colorectal Cancer Treatments and Studies
- CRISPR and Genetic Engineering
- Monoclonal and Polyclonal Antibodies Research
- Neuroblastoma Research and Treatments
University of Milano-Bicocca
2016-2025
Azienda Ospedaliera San Gerardo
2016-2025
Istituti di Ricovero e Cura a Carattere Scientifico
2023-2025
ASST Melegnano e della Martesana
2021-2022
University of Milan
2021
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
2019
Associazione Nazionale Medici Cardiologi Ospedalieri
2002-2017
LUCA School of Arts
2017
University Hospital Regensburg
2014
Centre Hospitalier Universitaire de Liège
2014
Resistance to imatinib represents an important scientific and clinical issue in chronic myelogenous leukemia. In the present study, effects of novel inhibitor SKI-606 on various models resistance were studied. proved be active Bcr-Abl several leukemia cell lines transfectants, with IC(50) values low nanomolar range, 1 2 logs lower than those obtained imatinib. Cells expressing activated forms KIT or platelet-derived growth factor receptor (PDGFR), two additional targets imatinib, unaffected...
Anaplastic lymphoma kinase (ALK)-positive lymphomas respond to chemotherapy, but relapses, which bear a poor prognosis, occur. Crizotinib inhibits ALK in vitro and vivo was administered as monotherapy 11 ALK+ patients who were resistant/refractory cytotoxic therapy. The overall response rate 10 of (90.9%; 95% confidence interval [CI] = 58.7% 99.8%). Disease status at the latest follow-up is follows: four are complete (CR) (months >21, >30, >35, >40) under continuous crizotinib...
Imatinib is effective for the treatment of chronic myeloid leukemia (CML). However even undetectable BCR‐ABL1 by Q‐RT‐PCR does not equate to eradication disease. Digital‐PCR (dPCR), able detect 1 positive cell out 10 7 , has been recently developed. The ISAV study a multicentre trial aimed at validating dPCR predict relapses after imatinib discontinuation in CML patients with Q‐RT‐PCR. under therapy since more than 2 years and PCR least 18 months were eligible. Patients monitored standard 36...
Abstract Colorectal malignancies are a leading cause of cancer-related death 1 and have undergone extensive genomic study 2,3 . However, DNA mutations alone do not fully explain malignant transformation 4–7 Here we investigate the co-evolution genome epigenome colorectal tumours at single-clone resolution using spatial multi-omic profiling individual glands. We collected 1,370 samples from 30 primary cancers 8 concomitant adenomas generated 1,207 chromatin accessibility profiles, 527 whole...
SETBP1 variants occur as somatic mutations in several hematological malignancies such atypical chronic myeloid leukemia and de novo germline the Schinzel-Giedion syndrome. Here we show that binds to gDNA AT-rich promoter regions, causing activation of gene expression through recruitment a HCF1/KMT2A/PHF8 epigenetic complex. Deletion two AT-hooks abrogates binding impairs target upregulation. Genes controlled by MECOM are significantly upregulated leukemias containing mutations. Gene ontology...
To dissect the mechanisms underlying inflation of variants in Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) genome, we present a large-scale analysis intra-host genomic diversity, which reveals that most samples exhibit heterogeneous architectures, due to interplay between host-related mutational processes and transmission dynamics. The decomposition minor profiles unveils three non-overlapping signatures related nucleotide substitutions likely ruled by APOlipoprotein B...
Acute myeloid leukemia (AML) is a hematological malignancy derived from neoplastic progenitor cells characterized by abnormal clonal proliferation and differentiation. Although novel therapeutic strategies have recently been introduced, the prognosis of AML remains unsatisfactory. So far, efficacy chimeric antigen receptor (CAR)-T therapy in has hampered several factors including poor accumulation blood-injected bone marrow (BM) niche, where chemotherapy-resistant leukemic stem reside. Thus,...
BCR/ABL (Breakpoint Cluster Region protein/Abelson tyrosine-protein kinase 1) domain (KD) mutations represent the most frequently described mechanism of resistance to treatment with tyrosine inhibitors (TKI) in patients chronic myeloid leukemia (CML). Mutations may impair TKI activity by directly or indirectly impairing drug binding protein. We report discovery three new mutations, L248R, T315V, and F317R identified two CML (L248R T315V) one patient Ph+ acute lymphoblastic (ALL) (F317R)....
Abstract Targeted therapy changed the standard of care in ALK-dependent tumors. However, resistance remains a major challenge. Lorlatinib is third-generation ALK inhibitor that inhibits most mutants resistant to current inhibitors. In this study, we utilize lorlatinib-resistant anaplastic large cell lymphoma (ALCL), non–small lung cancer (NSCLC), and neuroblastoma lines vitro vivo investigate acquisition its underlying mechanisms. ALCL cells acquired compound mutations G1202R/G1269A...
NKG2A expression identifies a subset of human Vd2 T cells exerting the highest antitumor effector functions
Background More than 50% of all patients with colorectal cancer (CRC) develop liver metastases (CLM), a clinical condition characterized by poor prognosis and lack reliable prognostic markers. Vδ1 cells are subset tissue-resident gamma delta (γδ) T lymphocytes endowed broad array antitumor functions showing natural high tropism for the liver. However, little is known about their impact in outcomes CLM. Methods We isolated human γδ from peripheral blood (PB) peritumoral (PT) tissue 93...
Ulcerative colitis (UC) is a chronic inflammatory disorder of unknown aetiology. Gut virome dysbiosis fundamental in UC progression, although its role the early phases disease far from fully understood. Therefore, we sought to investigate virome-associated protein encoded by
ALK is a tyrosine kinase receptor involved in broad range of solid and hematologic tumors. Among 70% to 80% ALK(+) anaplastic large cell lymphomas (ALCL) are caused by the aberrant oncogenic fusion protein NPM-ALK. Crizotinib was first clinically relevant inhibitor, now approved for treatment late-stage metastatic cases lung cancer. However, patients frequently develop drug resistance Crizotinib, mainly due appearance point mutations located domain. Fortunately, other inhibitors available...
We introduce VERSO, a two-step framework for the characterization of viral evolution from sequencing data genomes, which is an improvement on phylogenomic approaches consensus sequences. VERSO exploits efficient algorithmic strategy to return robust phylogenies clonal variant profiles, also in conditions sampling limitations. It then leverages frequency patterns characterize intra-host genomic diversity samples, revealing undetected infection chains and pinpointing variants likely involved...
Abstract The investigation of genetic forms juvenile neurodegeneration could shed light on the causative mechanisms neuronal loss. Schinzel-Giedion syndrome (SGS) is a fatal developmental caused by mutations in SETBP1 gene, inducing accumulation its protein product. SGS features multi-organ involvement with severe intellectual and physical deficits due, at least part, to early neurodegeneration. Here we introduce human model that displays disease-relevant phenotypes. We show neural...
Many large national and transnational studies have been dedicated to the analysis of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) genome, most which focused on missense nonsense mutations. However, approximately 30 per cent SARS-CoV-2 variants are synonymous, therefore changing target codon without affecting corresponding protein sequence. By performing a large-scale sequencing data generated from almost 400,000 samples, we show that silent mutations increasing similarity...
Anaplastic lymphoma kinase (ALK) tyrosine inhibitors (TKIs) show potent efficacy in several ALK-driven tumors, but the development of resistance limits their long-term clinical impact. Although mechanisms have been studied extensively non–small cell lung cancer, they are poorly understood anaplastic large (ALCL). Here, we identify a survival pathway supported by tumor microenvironment that activates phosphatidylinositol 3-kinase γ (PI3K-γ) signaling through C-C motif chemokine receptor 7...