A5067794159- Platelet Disorders and Treatments
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Cell Adhesion Molecules Research
- Chronic Myeloid Leukemia Treatments
- Hematopoietic Stem Cell Transplantation
- Acute Myeloid Leukemia Research
- Blood properties and coagulation
- Antiplatelet Therapy and Cardiovascular Diseases
- Eosinophilic Disorders and Syndromes
- Proteoglycans and glycosaminoglycans research
- Blood groups and transfusion
- Multiple Myeloma Research and Treatments
- Silk-based biomaterials and applications
- Erythrocyte Function and Pathophysiology
- Immunodeficiency and Autoimmune Disorders
- Periodontal Regeneration and Treatments
- Kruppel-like factors research
- 3D Printing in Biomedical Research
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Heparin-Induced Thrombocytopenia and Thrombosis
- Renal Diseases and Glomerulopathies
- Glycosylation and Glycoproteins Research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Chronic Lymphocytic Leukemia Research
- Protease and Inhibitor Mechanisms
University of Pavia
2016-2025
Tufts University
2016-2025
Istituti di Ricovero e Cura a Carattere Scientifico
2013-2022
Foundation Center
2017-2022
Policlinico San Matteo Fondazione
1997-2022
Laboratoire de Biochimie
2020
Medford Radiology Group
2015
Polaris (United States)
2011
Walther Cancer Foundation
1999-2009
Centro Cardiologico Monzino
2008
Background— Brain natriuretic peptide (BNP) is a marker of ventricular dysfunction and can be used to assess prognosis in heart failure after myocardial infarction. Heart involvement the most important prognostic factor causes death almost all patients with light-chain amyloidosis (AL). We investigated value NT-proBNP its utility monitoring amyloid dysfunction. Methods Results— was quantified at diagnosis 152 consecutive seen coordinating center Italian Amyloidosis Study Group (Pavia) from...
A quarter of patients with essential thrombocythemia or primary myelofibrosis carry a driver mutation CALR, the calreticulin gene. 52-bp deletion (type 1) and 5-bp insertion 2 mutation) are most frequent variants. These indels might differentially impair calcium binding activity mutant calreticulin. We studied relationship between subtype biological/clinical features disease. Thirty-two different types CALR variants were identified in 311 patients. Based on their predicted effect C-terminal,...
Point mutations in the 5′ UTR of ankyrin repeat domain 26 (ANKRD26) are associated with familial thrombocytopenia 2 (THC2) and a predisposition to leukemia. Here, we identified underlying mechanisms ANKRD26-associated thrombocytopenia. Using megakaryocytes (MK) isolated from THC2 patients healthy subjects, demonstrated that THC2-associated ANKRD26 resulted loss runt-related transcription factor 1 (RUNX1) friend leukemia integration (FLI1) binding. RUNX1 FLI1 binding at subjects led silencing...
Megakaryocytes associate with the bone marrow vasculature where they convert their cytoplasm into proplatelets that protrude through vascular endothelium lumen and release platelets. The extracellular matrix (ECM) microenvironment plays a critical role in regulating these processes. In this work we demonstrate that, among ECM components, fibronectin, type IV collagen, laminin are most abundant around sinusoids constitute pericellular surrounding megakaryocytes. Most importantly, report, for...
ETV6-related thrombocytopenia is an autosomal dominant that has been recently identified in a few families and suspected to predispose hematologic malignancies. To gain further information on this disorder, we searched for ETV6 mutations the 130 with inherited of unknown origin from our cohort 274 consecutive pedigrees familial thrombocytopenia. We 20 patients seven pedigrees. They have five different variants, including three novel affecting highly conserved E26 transformation-specific...
Abstract Mechanisms through which mature megakaryocytes (Mks) and their progenitors sense the bone marrow extracellular matrix to promote lineage differentiation in health disease are still partially understood. We found PIEZO1, a mechanosensitive cation channel, be expressed mouse human Mks. Human mutations PIEZO1 have been described associated with blood cell disorders. Yet, role for megakaryopoiesis proplatelet formation has never investigated. Here, we show that activation of increases...
Activated platelets and circulating platelet-leukocyte aggregates (PLA) are significantly higher in patients with unstable angina than those stable (SA). Platelets from healthy subjects express TF on activation. The aim of this study was to investigate the expression PLA, platelets, monocytes acute coronary syndrome (ACS) compared SA (Controls).We enrolled 26 consecutive ACS, 29 SA, 25 Controls. A greater number total positive platelet-monocyte found by flow cytometry blood ACS either...
Eltrombopag is a small, non-peptide thrombopoietin mimetic that has been approved for increasing platelet count not only in immune thrombocytopenia and Hepatitis C virus-related thrombocytopenia, but also aplastic anemia. Moreover, this drug under investigation counts myelodysplastic syndromes. Despite current clinical practice, the mechanisms governing eltrombopag's impact on human hematopoiesis are largely unknown, part due to impossibility of using traditional vivo models. To investigate...
Platelet release by megakaryocytes is regulated a concert of environmental and autocrine factors. We previously showed that constitutively released adenosine diphosphate human leads to platelet production. Here we show elicits, in megakaryocytes, an increase cytosolic calcium concentration, followed plateau, which lowered the absence extracellular calcium, suggesting involvement Store-Operated Calcium Entry. Indeed, demonstrate express major candidates mediate Entry, stromal interaction...
Hierarchical molecular assembly is a fundamental strategy for manufacturing protein structures in nature. However, to translate this natural into advanced digital like three-dimensional (3D) printing remains technical challenge. This work presents 3D technique with silk fibroin address challenge, by rationally designing an aqueous salt bath capable of directing the hierarchical molecules. technique, conducted under and ambient conditions, results proteinaceous architectures characterized...
Interactions of malignant multiple myeloma (MM) plasma cells (MM-cells) with the microenvironment control MM-cell growth, survival, drug-resistance and dissemination. As in MM microvascular density increases bone marrow (BM), we investigated whether BM endothelial (MMECs) disease progression via junctional adhesion molecule A (JAM-A). Membrane cytoplasmic JAM-A levels were upregulated MMECs 111 newly diagnosed (NDMM) 201 relapsed-refractory (RRMM) patients compared to monoclonal gammopathy...
Background The mechanism by which megakaryocytes (Mks) proliferate, differentiate, and release platelets into circulation are not well understood. Growing evidence indicates that a complex regulatory mechanism, involving cellular interactions, composition of the extracellular matrix physical parameters such as oxygen tension, may contribute to quiescent or permissive microenvironment related Mk differentiation maturation within bone marrow. Methodology/Principal Findings Differentiating...
MYH9-related disease (MYH9-RD) is an autosomal-dominant thrombocytopenia caused by mutations of MYH9, the gene for heavy chain myosin-IIA. Pathogenesis MYH9-RD unknown. Recent studies in mice demonstrated that myosin-IIA inhibitor proplatelet formation (PPF), and suggested it could be involved suppression PPF exerted megakaryocyte adhesion to type I collagen, which regulates timing platelet release within bone marrow. However, consequences on heterozygous causative have never been...
Platelets are specialized cells produced by megakaryocytes in the bone marrow that represent first defense against hemorrhage, yet they also play a pathological role thrombosis, inflammation, and cancer. Millions of platelet transfusions conducted each year, supply this blood component is limited. There many diseases where production or function impaired with severe consequences for patients. With such clinical need, new insight into formation platelets would have major impact on patients...
The interaction of megakaryocytes with matrix proteins the osteoblastic and vascular niche is essential for megakaryocyte maturation proplatelet formation. Fibrinogen present in fibrinogen receptor α(IIb)β(3) abundantly expressed on megakaryocytes, however role between formation humans not yet fully understood. We have recently reported a novel congenital macrothrombocytopenia associated heterozygous mutation β(3) subunit α(IIb)β(3). origin thrombocytopenia this condition remains unclear may...
Megakaryocytes (MK) in the bone marrow (BM) are immersed a network of extracellular matrix components that regulates platelet release into circulation. Combining biological and bioengineering approaches, we found activation transient receptor potential cation channel subfamily V member 4 (TRPV4), mechano-sensitive ion channel, is induced upon MK adhesion on softer matrices. This response promoted production by triggering cascade events lead to calcium influx, β1 integrin internalization, Akt...