Benedetta Peruzzi

Azienda Ospedaliero Universitaria Careggi · General Laboratory

Introduction Recently, a flow cytometric (FC) based test has been developed for detection of circulating fetal cells to replace the less accurate and reproducible Kleihauer-Betke test. FC test is easier to perform, it can distinguish the origin of fetal cells, but it is expensive and available in highly specialized laboratories. We evaluated the in...

Background: NPM1 mutations represent the most common genetic alteration in adult acute myeloid leukemia (AML), often in co-occurrence with FLT3-ITD and mutations in genes influencing DNA methylation ( DNMT3A, IDH1, IDH2 and TET2). Whether these genetic alterations correlate with distinct immunophenotypic and clinical features is still a matter of d...

Background: CEBPA-mutated acute myeloid leukemia (AML) is a separate entity in the updated WHO and ICC classifications. Previously identified by double mutations, the clinical profile and favorable outcome were correlated with in-frame mutations in bZIP domain. Beyond mutations recurrent in myeloid neoplasms (involving TET2, FLT3, NRAS), CEBPA-muta...

Measurable residual disease (MRD) is a powerful predictor of outcome in acute myeloid leukemia (AML). In the early phases of treatment, MRD refines initial disease risk stratification and is used for the allocation to allogeneic transplant (HSCT). Despite its well-established role, a relatively high fraction of patients eventually relapses albeit a...

The identification of mature T cell neoplasms by flow cytometry is often challenging, due to overlapping features with reactive T cells and limitations of currently available T cell clonality assays. The description of an antibody specific for one of two mutually exclusive T cell receptor (TCR) β-chain constant regions (TRBC1) provides an opportuni...

Background and Purpose Waning immunity and the surge of SARS-CoV-2 variants are responsible for breakthrough infections, i.e., infections in fully vaccinated individuals. Although the majority of vaccinated infected subjects report mild or no symptoms, some others require hospitalization. The clinical and immunological features of vaccinated hospit...

Relapsing-remitting multiple sclerosis (RRMS) is a demyelinating disease in which pathogenesis T cells have a major role. Despite the unknown etiology, several risk factors have been described, including a strong association with human leukocyte antigen (HLA) genes. Recent findings showed that HLA class I-G (HLA-G) may be tolerogenic in MS, but fur...

Prognostic modeling in myelofibrosis (MF) has classically pursued the integration of informative clinical and hematological parameters to separate patients' categories with different outcomes. Modern stratification includes also genetic data from karyotype and mutations. However, some poorly standardized variables, as peripheral blood (PB) blast co...

Background Waning immunity and the surge of SARS-CoV-2 variants are responsible for breakthrough infections, i.e. infections in fully vaccinated individuals. Although the majority of vaccinated infected subjects reports mild or no symptoms, some others require hospitalization. The clinical and immunological features of vaccinated hospitalized COVID...

Context Standard treatment of anemia in lower-risk myelodysplastic syndromes (LR-MDS) is based on erythropoietic-stimulating agents (ESAs), but some patients are primary refractory (PR) or lose response (secondary refractory, SR). High serum erythropoietin (sEPO) is the main negative predictor, and treatment of ESA-resistant anemia is challenging,...

Context Relapsed/refractory (R/R) acute myeloid leukemia (AML) is an unmet medical need. Recently, a number of small retrospective studies evaluated the outcomes of R/R AML patients treated with venetoclax as single agent or in combinations, reporting encouraging results. Objective Our aim was to retrospectively analyze the clinical characteristic...

Relapsed/refractory (R/R) acute myeloid leukemia (AML) is a largely unmet medical need, owing to the lack of standardized, effective treatment approaches, resulting in an overall dismal outcome. The only curative option for R/R AML patients is allogeneic hematopoietic stem cell transplantation (HSCT) which is only applicable in a fraction of patien...

Overwhelming inflammatory reactions contribute to respiratory distress in patients with COVID-19. Ruxolitinib is a JAK1/JAK2 inhibitor with potent anti-inflammatory properties. We report on a prospective, observational study in 34 patients with COVID-19 who received ruxolitinib on a compassionate-use protocol. Patients had severe pulmonary disease...

T-cell receptor (TCR)-Vβ repertoire analysis is a sensitive method for detection of T-cell clonality. This type of analysis has been used for studying selective T-cell responses in autoimmune disease, alloreactivity in transplantation, and protective immunity against microbial and tumor antigens and in neoplastic T cells. Here, we describe the flow...

Post-Transplant Lymphoproliferative Disease (PTLD) following both Solid Organ Transplantation (SOT) and Hematopoietic Stem Cell Transplantation (HSCT) is a rare life-threatening complication. The majority of PLTDs are associated to Epstein Bar Virus (EBV) [1] reactivation, usually in the early phase [2] after transplant, when the patient is severel...

Simple Summary The prognostic role of multi-lineage dysplasia is still debated in acute myeloid leukemia. The aim of our work was to study dysplasia by a technique alternative to the conventional morphological method, which is multi-parameter flow cytometry. To this end, we used an immune-phenotypic score (IPS), able to estimate dysplasia by the ex...

SARS‐CoV‐2 is responsible for a new infectious disease (COVID‐19) in which individuals can either remain asymptomatic or progress from mild to severe clinical conditions including acute respiratory distress syndrome and multiple organ failure. The immune mechanisms that potentially orchestrate the pathology in SARS‐CoV‐2 infection are complex and o...

Background: Coronavirus disease 19 (COVID-19) is an emerging infectious disease caused by SARS-CoV-2. Anti-viral immune response is crucial to achieve pathogen clearance, however in some patients an excessive and aberrant host immune response can lead to an acute respiratory distress syndrome. The comprehension of the mechanisms that regulate path...

Natalizumab (NTZ) and autologous hematopoietic stem cell transplantation (AHSCT) are two successful treatments for relapsing-remitting multiple sclerosis (RRMS), an autoimmune T-cell-driven disorder affecting the central nervous system that is characterized by relapses interspersed with periods of complete or partial recovery. Both RRMS treatments...

Background. MPN are clonal disorders of hematopoietic stem cell (HSC) that include polycythemia vera (PV), essential thrombocytemia (ET) and myelofibrosis (MF), either secondary to ET-PV, or primary (PMF), including pre-fibrotic (pre-PMF) and overt. In MF, multi-lineage dysplasia (MLD) of varying degree can be detected by morphologic analysis of bo...

Background NPM1‐mutated acute myeloid leukemia is a clinically heterogeneous disease entity encompassing different risk categories; despite growing knowledge on the impact of concurrent mutations, part of this biological and clinical heterogeneity is still unexplained. To date, a comprehensive description of the immunophenotypic landscape in NPM1 m...

Mutations in CCAAT/enhancer binding protein α (CEBPA) occur in 5-10% of cases of acute myeloid leukemia. CEBPA-doublemutated cases usually bear bi-allelic N- and C-terminal mutations and are associated with a favorable clinical outcome. Identification of CEBPA mutants is challenging because of the variety of mutations, intrinsic characteristics of...

Multicenter evaluation of blood cell counts on 8 automated hematology analyzers. The cellular analysis performed on hematology analyzers is based on the interaction of cells with electrical or optical signals. The heterogeneity of adopted methods and technologies by different analyzers can translate in a lack of homogeneity in analytical performanc...

Multicenter evaluation of blood cell counts on 8 automated hematology analyzers. The cellular analysis performed on hematology analyzers is based on the interaction of cells with electrical or optical signals. The heterogeneity of adopted methods and technologies by different analyzers can translate in a lack of homogeneity in analytical performanc...

The cellular analysis performed on hematology analyzers is based on the interaction of cells with electrical or optical signals. The heterogeneity of adopted methods and technologies by different analyzers can translate in a lack of homogeneity in analytical performance. This study compares 8 hematological analyzers vs. optical microscopy (OM) and,...

Fingolimod affords protection from MS by sequestering lymphocytes in secondary lymphoid organs via down regulation of their sphingosine 1 phosphate receptor (S1P1). Unexpectedly, accumulating evidence indicates that patients who discontinue fingolimod treatment may be at risk of rehearsal of magnetic resonance (MR) and clinical disease activity, so...

The presence of multi-lineage dysplasia (MLD) by morphology at diagnosis in acute myeloid leukemia (AML) defines a separate subset in WHO classification with still debated prognostic value. A major controversy concerns MLD role in NPM1-mutated (NPM1+) AML, in turn correlating with good prognosis. We used flow cytometry (FC), an emerging technique f...

Background and purpose: Immune events sustaining dendritic cell (DC)-dependent epitope spreading (ES) are of key relevance to the development of relapses during multiple sclerosis (MS). Although no drugs are currently available to target ES, its inhibition would represent a major advancement in MS therapy. Inhibitors of the enzyme PARP-1 afford pr...

BACKGROUND: Certification rules of point-of-care testing (POCT) require periodic evaluation of performance of POCT devices using control material different from that used daily. The aim of this report was to verify the reliability and the labor required for a quality assessment program operated by the laboratory. METHODS: Two pools (L1 and L2) of s...

Pleural effusion as the first clinical manifestation of acute lymphoblastic leukemia (ALL) is a relatively rare event. An early and accurate diagnosis of this clinical picture is very important for adequate patient management. We report the atypical onset of T-lineage ALL in a 31-year-old man. The patient was admitted to the emergency room due to l...

Complement blockade by eculizumab is clinically effective in hemolytic Paroxysmal Nocturnal Hemoglobinuria. However, the response is variable and some patients remain red blood cell transfusion-dependent. In 72 patients with hemolytic Paroxysmal Nocturnal Hemoglobinuria on eculizumab we tested the hypothesis that response may depend on genetic poly...

Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a unique disorder caused by a PIG-A gene mutation in a stem cell clone. Its clinical picture can sometimes make challenging the distinction from other disorders, and especially from myelodysplastic syndromes (MDS), since both diseases correlate with cytopenias and morphological abnormalities...

Germ-line mutation rate has been regarded classically as a fundamental biological parameter, as it affects the prevalence of genetic disorders and the rate of evolution. Somatic mutation rate is also an important biological parameter, as it may influence the development and/or the course of acquired diseases, particularly of cancer. Estimates of th...

Distribution of ƒ in a population of 142 healthy individuals. In this scattergram each dot represent the ƒ value of one healthy individual. When more than one measurement was available the average ƒ is shown. (PDF)

983 Eculizumab, a monoclonal antibody that binds to the complement component C5, controls intravascular hemolysis in PNH patients and causes significant clinical improvement. However, the extent to which patients respond is variable in terms of hemoglobin levels, and some patients remain red blood cell (RBC) transfusion-dependent in spite of regula...

Increased microvessel density contributes to abnormal bone marrow and spleen microenvironment in myelofibrosis (MF). Taking advantage from the JAK2V617F mutation as a marker of malignancy, we investigated, in patients bearing the mutation in their granulocytes and undergoing splenectomy for therapeutical reasons, whether splenic ECs obtained either...

Hepatocyte growth factor (HGF) and vascular endothelial cell growth factor (VEGF) regulate normal development and homeostasis and drive disease progression in many forms of cancer. Both proteins signal by binding to receptor tyrosine kinases and heparan sulfate (HS) proteoglycans on target cell surfaces. Basic residues comprising the primary HS bin...

Several immunological fecal occult blood tests (FOBT) are currently available for colorectal cancer (CRC) screening. We compared the HM Jack (Jack) (Kiowa, Japan), with the OC-Hemodia (OC) (Eiken, Japan) in use in the Florence screening program. Aims of the study were: (i) to investigate the diagnostic performance and the best cutoff value for Jack...

10528 Background: Hepatocyte growth factor (HGF) stimulates cell proliferation, motility, and morphogenesis upon binding to the receptor tyrosine kinase Met and cell surface heparan sulfate (HS) glycans. NK1 is a truncated HGF isoform consisting of the N-terminal (N) and first kringle (K1) domains of full-length HGF that stimulates all major HGF bi...

Hepatocyte growth factor (HGF) stimulates cell proliferation, motility, and morphogenesis upon binding to the receptor tyrosine kinase Met and cell surface heparan sulfate (HS) glycans. NK1 is a truncated HGF isoform consisting of the N-terminal (N) and first kringle (K1) domains of full-length HGF that stimulates all major HGF biological activitie...

Complement C3 'slow' and 'fast' allotypes are associated with immune-mediated disorders and may affect the outcome of renal transplantation. We report a tetra-primer amplification refractory mutation system PCR (T-ARMS-PCR) that provides a rapid, reproducible and cost-effective method to genotype both complement C3 'slow' and 'fast' alleles by a si...

Recently, carbonic anhydrase (CA) inhibitors have been proposed as a potential new class of antitumor agents. The aim of this study was to evaluate the antitumor activity of three CA inhibitors, namely acetazolamide (AZ) and two newly synthesized aromatic sulfonamides with high affinity for CA IX, 2-(4-sulfamoylphenyl-amino)-4,6-dichloro-1,3,5-tria...

Mutations are an inherent risk of cell duplication. On one hand, inheritable mutations are the driving force of biological evolution; on the other hand, their accumulation in somatic cells plays a key role in the development of cancer. The frequency of mutants (f) and the rate of mutation (mu) are biological features of any cell population: their m...

The urgent need for effective therapies for patients with advanced renal cell carcinoma (RCC), fewer than 20% of whom will survive more than 2 years, has led to the identification of critical genetic determinants and associated molecular pathways contributing to RCC oncogenesis, progression, and spread. Among the signaling pathways dysregulated in...

We have shown previously that a potent synthetic antagonist of growth factor receptor-bound protein 2 (Grb2) Src homology 2 (SH2) domain binding (1) blocks growth factor stimulated motility, invasion, and angiogenesis in cultured cell models, as well as tumor metastasis in animals. To characterize the selectivity of 1 for the SH2 domain of Grb2 ove...

Loss of von Hippel-Lindau (VHL) tumor suppressor gene function occurs in familial and most sporadic renal cell carcinoma (RCC), resulting in the aberrant expression of genes that control cell proliferation, invasion and angiogenesis. The molecular mechanisms by which VHL loss leads to tumorigenesis are not yet fully defined. The VHL gene product, p...

Loss of von Hippel–Lindau (VHL) tumor suppressor gene function occurs in familial and most sporadic clear cell renal cell carcinoma (RCC), resulting in the aberrant expression of genes that control cell proliferation, invasion, and angiogenesis. The molecular mechanisms by which VHL loss leads to tumorigenesis are not yet fully defined. VHL loss ha...

On binding to the cell surface receptor tyrosine kinase (TK) known as c-Met, hepatocyte growth factor (HGF) stimulates mitogenesis, motogenesis, and morphogenesis in a wide range of cellular targets including, epithelial and endothelial cells, hematopoietic cells, neurons, melanocytes, and hepatocytes. These pleiotropic actions are fundamentally im...

Growth factor receptor-bound 2 (Grb2) is a ubiquitously expressed adapter protein that provides a critical link between cell surface growth factor receptors and the Ras signaling pathway. As such, it has been implicated in the oncogenesis of several important human malignancies. In addition to this function, research over the last decade has reveal...

Inhibition of angiogenesis is a major target in the fight against cancer and other diseases. Although the effects of static magnetic fields on cancer development and cell growth have been investigated, effects on angiogenesis have received no attention so far. In this study we report the effects on angiogenesis of exposure to 0.2 T static magnetic...

Human endogenous plasma heparin associates with proteins that mask its anticoagulant activity. This association persists after exhaustive proteolysis of plasma, and resulting peptide/heparin complexes have no anticoagulant activity. Looking for functions other than inhibition of coagulation, we considered that commercial preparations of heparin fro...

We evaluated the effects of urban air pollutants on human nasal mucosa over an 8-month period on 102 subjects living in Florence, Tuscany, Italy. A group of subjects living in a city with a lower level of pollution (Sassari, Sardinia, Italy) was also analyzed. Nasal mucosa cells were harvested by brushing, a noninvasive procedure. Half of the cells...

Human skin fibroblasts were exposed to 0.2 T static magnetic field generated by a magnetic resonance tomograph. After 1h exposure, cell morphology was modified in association with a concomitant decrease in the expression of some sugar residues of glycoconjugates. Study of cell proliferation and mitogenic signal transduction showed a decrease of thy...