Human γδ T-Cells: From Surface Receptors to the Therapy of High-Risk Leukemias

γδ T lymphocytes are potent effector cells, capable of efficiently killing tumor and leukemia cells. Their activation is mediated by γδ T-cell receptor (TCR) and by activating receptors shared with NK cells (e.g., NKG2D and DNAM-1). γδ T-cell triggering occurs upon interaction with specific ligands, including phosphoantigens (for Vγ9Vδ2 TCR), MICA-B and UL16 binding protein (for NKG2D), and PVR and Nectin-2 (for DNAM-1). They also respond to cytokines undergoing proliferation and release of cytokines/chemokines. Although at the genomic level γδ T-cells have the potential of an extraordinary TCR diversification, in tissues they display a restricted repertoire. Recent studies have identified …

Symptomatic hypoglycemia in children receiving oral purine analogues for treatment of childhood acute lymphoblastic leukemia

Background Antimetabolite-based continuation therapy is commonly used for childhood acute lymphoblastic leukemia (ALL) and hypoglycemia after prolonged fasting has been recently reported. We have found that spontaneous, symptomatic hypoglycemia (SH) may also occur in such patients. Procedure Between 1995 and 1999, patients treated according to the AIEOP-ALL-95 study received BFM-type intensive chemotherapy; mercaptopurine (6-MP) was given (60 mg/m2/days, orally for 14 days) during the second part of induction and during consolidation therapy (25 mg/m2/day, orally for 8 weeks); thioguanine (6-TG) was given during reinduction therapy with protocol II (60 mg/m2/day, orally for 14 days); contin…

Looking for pathways related to COVID-19 phenotypes: Confirmation of pathogenic mechanisms by SARS-CoV-2 - Host interactome

AbstractIn the last months, many studies have clearly described several mechanisms of SARS-CoV-2 infection at cell and tissue level. Host conditions and comorbidities were identified as risk factors for severe and fatal disease courses, but the mechanisms of interaction between host and SARS-CoV-2 determining the grade of COVID- 19 severity, are still unknown.We provide a network analysis on protein–protein interactions (PPI) between viral and host proteins to better identify host biological responses, induced by both whole proteome of SARS-CoV-2 and specific viral proteins. A host-virus interactome was inferred on published PPI, using an explorative algorithm (Random Walk with Restart) tri…

Road Traffic Pollution and Childhood Leukemia: A Nationwide Case-control Study in Italy

Background The association of childhood leukemia with traffic pollution was considered in a number of studies from 1989 onwards, with results not entirely consistent and little information regarding subtypes. Aim of the study We used the data of the Italian SETIL case-control on childhood leukemia to explore the risk by leukemia subtypes associated to exposure to vehicular traffic. Methods We included in the analyses 648 cases of childhood leukemia (565 Acute lymphoblastic–ALL and 80 Acute non lymphoblastic-AnLL) and 980 controls. Information on traffic exposure was collected from questionnaire interviews and from the geocoding of house addresses, for all periods of life of the children. Re…

COVID-19 disease - Temporal analyses of complete blood count parameters over course of illness, and relationship to patient demographics and management outcomes in survivors and non-survivors: a longitudinal descriptive cohort study

Background Detailed temporal analyses of complete (full) blood count (CBC) parameters, their evolution and relationship to patient age, gender, co-morbidities and management outcomes in survivors and non-survivors with COVID-19 disease, could identify prognostic clinical biomarkers. Methods From 29 January 2020 until 28 March 2020, we performed a longitudinal cohort study of COVID-19 inpatients at the Italian National Institute for Infectious Diseases, Rome, Italy. 9 CBC parameters were studied as continuous variables [neutrophils, lymphocytes, monocytes, platelets, mean platelet volume, red blood cell count, haemoglobin concentration, mean red blood cell volume and red blood cell distribu…

A single high dose of idarubicin combined with high-dose ARA-C for treatment of first relapse in childhood ‘high-risk’ acute lymphoblastic leukaemia: a study of the AIEOP group

The outcome of children with acute lymphoblastic leukaemia (ALL) and early relapse remains unsatisfactory. In January 1995, the AIEOP (Associazione Italiana di Oncologia ed Ematologia Pediatrica) group opened a trial for children with ALL in first isolated or combined bone marrow relapse defined at high risk according to the length of first remission and the immunophenotype. The treatment plan included the combination of a single high-dose idarubicin and high-dose cytarabine as induction therapy followed by an intensive consolidation and stem cell transplant (SCT). In total, 100 children from 16 Italian centres were enrolled; 80 out of the 99 evaluable patients (81%) achieved second complet…

The unbalanced p53/SIRT1 axis may impact lymphocyte homeostasis in COVID-19 patients

Abstract Background/objectives A dysregulated inflammatory profile plays an important role in coronavirus disease-2019 (COVID-19) pathogenesis. Moreover, the depletion of lymphocytes is typically associated with an unfavourable disease course. We studied the role and impact of p53 and deacetylase Sirtuin 1 (SIRT1) on lymph-monocyte homeostasis and their possible effect on T and B cell signalling. Methods Gene expression analysis and flow cytometry were performed on peripheral blood mononuclear cells (PBMC) of 35 COVID-19 patients and 10 healthy donors (HD). Inflammatory cytokines, the frequency of Annexin+ cells among CD3+ T cells and CD19+ B cell subsets were quantified. Results PBMC from …

An Inflammatory Profile Correlates With Decreased Frequency of Cytotoxic Cells in Coronavirus Disease 2019

Abstract Increased production of inflammatory cytokines and myeloid-derived suppressor cells occurs in patients with coronavirus disease 2019. These inversely correlated with perforin-expressing natural killer (NK) and CD3+ T cells. We observed a lower number of perforin-expressing NK cells in intensive care unit (ICU) patients compared with non-ICU patients, suggesting an impairment of the immune cytotoxic arm as a pathogenic mechanism.

Childhood high-risk acute lymphoblastic leukemia in first remission: results after chemotherapy or transplant from the AIEOP ALL 2000 study

The outcome of high-risk (HR) Acute Lymphoblastic Leukemia (ALL) patients enrolled in AIEOP-BFM ALL 2000 study (NCT00613457) in Italy is described. Overall, 1999 Philadelphia negative ALL patients entered the study. HR criteria were: minimal residual disease (MRD) levels ≥10-3 at day 78 (HR-MRD), no complete remission (no-CR) at day 33, t(4;11) translocation, Prednisone Poor Response (PPR). Treatment (2 years) included protocol I, 3 polychemotherapy blocks, delayed intensification (protocol IIx2 or IIIx3), cranial radiotherapy, maintenance. 312 HR patients (15.6% of the total) had 5-year event-free survival (EFS) and overall survival (OS) of 58.9%(SE 2.8) and 68.9%(2.6). In hierarchical ord…

COVID-19: viral–host interactome analyzed by network based-approach model to study pathogenesis of SARS-CoV-2 infection

AbstractBackgroundEpidemiological, virological and pathogenetic characteristics of SARS-CoV-2 infection are under evaluation. A better understanding of the pathophysiology associated with COVID-19 is crucial to improve treatment modalities and to develop effective prevention strategies. Transcriptomic and proteomic data on the host response against SARS-CoV-2 still have anecdotic character; currently available data from other coronavirus infections are therefore a key source of information.MethodsWe investigated selected molecular aspects of three human coronavirus (HCoV) infections, namely SARS-CoV, MERS-CoV and HCoV-229E, through a network based-approach. A functional analysis of HCoV-hos…

Lessons from the COVID-19 Pandemic—Unique Opportunities for Unifying, Revamping and Reshaping Epidemic Preparedness of Europe’s Public Health Systems

Additional file 2 of COVID-19: viral–host interactome analyzed by network based-approach model to study pathogenesis of SARS-CoV-2 infection

Additional file 2: Figure S1. Pairwise distances along 259 full length CoV genomes. In the bottom of picture, indicative gene positioning along CoVs genomes is reported. The list of all considered genomes is reported in Additional file 1: Table S1. Figure S2. 3D structure of S-glycoprotein of SARS-CoV-2 and comparison with the ortholog from HCoV-229E, SARS-CoV, and MERS-CoV. Lateral (a) and superior (b) representation of SARS-CoV-2 S-glycoprotein, deducted for the sequence of patient INMI1 (MT066156.1). Each subunit chain has a different color. Structure comparison of S-glycoprotein subunit between: HCoV-229E and SARS-CoV-2, in purple and blue respectively (c); SARS-CoV and SARS-CoV-2, in r…

Predictors of Early Death in Childhood Acute Promyelocytic Leukemia: Results of an International Retrospective Study

Abstract Background: Acute promyelocytic leukemia (APL) is a rare subtype of childhood acute myeloid leukemia (AML). Bleeding complications occur in 80% of patients at diagnosis and contribute to a higher incidence of early death (ED) in APL compared to other AML subtypes. However, estimates of ED in pediatric APL are imprecise and factors associated with ED in children with APL are unknown. Objectives: To determine the incidence and predictors of ED, defined as death within 60 days from presentation, in childhood APL. Methods: We conducted a retrospective international analysis of children diagnosed with APL between January 1993 and December 2013. The study included 236 patients from the I…

Different Innate and Adaptive Immune Responses to SARS-CoV-2 Infection of Asymptomatic, Mild, and Severe Cases

Abstract Background SARS-CoV-2 is a novel coronavirus, not encountered before by humans. The wide spectrum of clinical expression of SARS-CoV-2 illness suggests that individual immune responses to SARS-CoV-2 play a crucial role in determining the clinical course after first infection. Immunological studies have focussed on patients with moderate to severe disease, demonstrating excessive inflammation in tissues and organ damage. We have studied the individual response to SARS-CoV-2 of asympromatic, mild and severe COVID-19 patients in order to investigate the role of innnate and adaptive immunity in determining the clinical course after first infection. Methods To understand the basis of th…

The prognostic value of biological markers in paediatric Hodgkin lymphoma

Abstract Background Many biological and inflammatory markers have been proposed as having a prognostic value at diagnosis of Hodgkin lymphoma (HL), but very few have been validated in paediatric patients. We explored the significance of these markers in a large population of 769 affected children. Patients and methods By using the database of patients enrolled in A.I.E.O.P. (Associazione Italiana di Emato-Oncologia Pediatrica) trial LH2004 for paediatric HL, we identified 769 consecutive patients treated with curative intent from 1st June 2004 to 1st April 2014 with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine), or hybrid COPP/ABV (cyclophosphamide, vincristine, prednisone, pr…

Additional file 1 of COVID-19: viral–host interactome analyzed by network based-approach model to study pathogenesis of SARS-CoV-2 infection

Additional file 1: Table S1. List of accession numbers of H-CoV. Table S2. List of genes selected by RWR algorithm for HCoV-229E, along with proximity score. Table S3. List of genes selected by RWR algorithm for SARS-CoV, along with proximity score. Table S4. List of genes selected by RWR algorithm for MERS-CoV, along with proximity score.