TY - JOUR T1 - Idiopathic neutropenia of infancy: Data from the Italian Neutropenia Registry. JF - Am J Hematol Y1 - 2019 A1 - Farruggia, Piero A1 - Fioredda, Francesca A1 - Puccio, Giuseppe A1 - Onofrillo, Daniela A1 - Russo, Giovanna A1 - Barone, Angelica A1 - Bonanomi, Sonia A1 - Boscarol, Gianluca A1 - Finocchi, Andrea A1 - Ghilardi, Roberta A1 - Giordano, Paola A1 - Ladogana, Saverio A1 - Lassandro, Giuseppe A1 - Luti, Laura A1 - Lanza, Tiziana A1 - Mandaglio, Rosalba A1 - Marra, Nicoletta A1 - Martire, Baldassare A1 - Mastrodicasa, Elena A1 - Motta, Milena A1 - Notarangelo, Lucia Dora A1 - Pillon, Marta A1 - Porretti, Laura A1 - Serafinelli, Jessica A1 - Trizzino, Angela A1 - Tucci, Fabio A1 - Veltroni, Marinella A1 - Verzegnassi, Federico A1 - Ramenghi, Ugo A1 - Dufour, Carlo AB -

Autoimmune neutropenia of infancy (AIN) is characterized by low risk of severe infection, tendency to spontaneously resolve and typically onset at ≤4-5 years of age; it is due to auto-antibodies whose detection is often difficult. In case of negativity of 4 antineutrophils autoantibody tests, after having excluded ethnic, postinfection, drug induced, or congenital neutropenia, according to the Italian guidelines the patients will be defined as affected by "idiopathic neutropenia" (IN). We describe the characteristics of 85 IN patients enrolled in the Italian neutropenia registry: they were compared with 336 children affected by AIN. The 2 groups were clinically very similar and the main differences were detection age (later in IN), length of disease (longer in IN) and, among recovered patients, age of spontaneous recovery: the median age at resolution was 2.13 years in AINs and 3.03 years in INs (P = .00002). At bivariate analysis among AIN patients earlier detection age (P = .00013), male sex (P = .000748), absence of leucopenia (P = .0045), and absence of monocytosis (P = .0419) were significantly associated with earlier recovery; in the IN group only detection age (P = .013) and absence of monocytosis (P = .0333) were significant. At multivariate analysis detection age and absence of monocytosis were independently significant (P = 6.7e-05 and 4.4e-03, respectively) in the AIN group, whereas in the IN group only detection age stayed significant (P = .013).

VL - 94 IS - 2 U1 - http://www.ncbi.nlm.nih.gov/pubmed/30456824?dopt=Abstract ER - TY - JOUR T1 - Loss-of-function mutations in cause a new form of inherited thrombocytopenia. JF - Blood Y1 - 2019 A1 - Marconi, Caterina A1 - Di Buduo, Christian A A1 - LeVine, Kellie A1 - Barozzi, Serena A1 - Faleschini, Michela A1 - Bozzi, Valeria A1 - Palombo, Flavia A1 - McKinstry, Spencer A1 - Lassandro, Giuseppe A1 - Giordano, Paola A1 - Noris, Patrizia A1 - Balduini, Carlo L A1 - Savoia, Anna A1 - Balduini, Alessandra A1 - Pippucci, Tommaso A1 - Seri, Marco A1 - Katsanis, Nicholas A1 - Pecci, Alessandro AB -

Inherited thrombocytopenias (ITs) are a heterogeneous group of disorders characterized by low platelet count that may result in bleeding tendency. Despite progress being made in defining the genetic causes of ITs, nearly 50% of patients with familial thrombocytopenia are affected with forms of unknown origin. Here, through exome sequencing of 2 siblings with autosomal-recessive thrombocytopenia, we identified biallelic loss-of-function variants in This gene encodes for a receptor-like PTP, PTPRJ (or CD148), which is expressed abundantly in platelets and megakaryocytes. Consistent with the predicted effects of the variants, both probands have an almost complete loss of PTPRJ at the messenger RNA and protein levels. To investigate the pathogenic role of PTPRJ deficiency in hematopoiesis in vivo, we carried out CRISPR/Cas9-mediated ablation of (the ortholog of human ) in zebrafish, which induced a significantly decreased number of CD41 thrombocytes in vivo. Moreover, megakaryocytes of our patients showed impaired maturation and profound defects in SDF1-driven migration and formation of proplatelets in vitro. Silencing of in a human megakaryocytic cell line reproduced the functional defects observed in patients' megakaryocytes. The disorder caused by mutations presented as a nonsyndromic thrombocytopenia characterized by spontaneous bleeding, small-sized platelets, and impaired platelet responses to the GPVI agonists collagen and convulxin. These platelet functional defects could be attributed to reduced activation of Src family kinases. Taken together, our data identify a new form of IT and highlight a hitherto unknown fundamental role for PTPRJ in platelet biogenesis.

VL - 133 IS - 12 U1 - http://www.ncbi.nlm.nih.gov/pubmed/30591527?dopt=Abstract ER - TY - JOUR T1 - Mutations of RUNX1 in families with inherited thrombocytopenia. JF - Am J Hematol Y1 - 2017 A1 - De Rocco, Daniela A1 - Melazzini, Federica A1 - Marconi, Caterina A1 - Pecci, Alessandro A1 - Bottega, Roberta A1 - Gnan, Chiara A1 - Palombo, Flavia A1 - Giordano, Paola A1 - Coccioli, Maria Susanna A1 - Glembotsky, Ana C A1 - Heller, Paula G A1 - Seri, Marco A1 - Savoia, Anna A1 - Noris, Patrizia KW - Adult KW - Blood Platelets KW - Cell Size KW - Child KW - Child, Preschool KW - Core Binding Factor Alpha 2 Subunit KW - Female KW - Frameshift Mutation KW - Genes, Dominant KW - Heterozygote KW - Humans KW - Introns KW - Leukemia, Myeloid, Acute KW - Male KW - Middle Aged KW - Mutation, Missense KW - Protein Domains KW - RNA Splice Sites KW - Sequence Deletion KW - Thrombocythemia, Essential KW - Thrombopoietin KW - Transcriptional Activation KW - Young Adult VL - 92 IS - 6 U1 - http://www.ncbi.nlm.nih.gov/pubmed/28240786?dopt=Abstract ER - TY - JOUR T1 - Are all cases of paediatric essential thrombocythaemia really myeloproliferative neoplasms? Analysis of a large cohort. JF - Br J Haematol Y1 - 2015 A1 - Randi, Maria L A1 - Geranio, Giulia A1 - Bertozzi, Irene A1 - Micalizzi, Concetta A1 - Ramenghi, Ugo A1 - Tucci, Fabio A1 - Notarangelo, Lucia D A1 - Ladogana, Saverio A1 - Menna, Giuseppe A1 - Giordano, Paola A1 - Consarino, Caterina A1 - Farruggia, Piero A1 - Zanazzo, Giulio A A1 - Fiori, Giovanni M A1 - Burnelli, Roberta A1 - Russo, Giovanna A1 - Jankovich, Momcilo A1 - Peroni, Edoardo A1 - Duner, Elena A1 - Basso, Giuseppe A1 - Fabris, Fabrizio A1 - Putti, Maria C KW - Adolescent KW - Adult KW - Amino Acid Substitution KW - Child KW - Child, Preschool KW - Cohort Studies KW - Female KW - Hematologic Neoplasms KW - Humans KW - Infant KW - Janus Kinase 2 KW - Male KW - Mutation, Missense KW - Neoplasm Proteins KW - Thrombocythemia, Essential AB -

Sporadic essential thrombocythaemia (ET) is rare in paediatrics, and the diagnostic and clinical approach to paediatric cases cannot be simply copied from experience with adults. Here, we assessed 89 children with a clinical diagnosis of ET and found that 23 patients (25·8%) had a clonal disease. The JAK2 V617F mutation was identified in 14 children, 1 child had the MPL W515L mutation, and 6 had CALR mutations. The monoclonal X-chromosome inactivation pattern was seen in six patients (two with JAK2 V617F and two with CALR mutations). The other 66 patients (74·2%) had persistent thrombocytosis with no clonality. There were no clinical or haematological differences between the clonal and non-clonal patients. The relative proportion of ET-specific mutations in the clonal children was much the same as in adults. The higher prevalence of non-clonal cases suggests that some patients may not have myeloproliferative neoplasms, with significant implications for their treatment.

VL - 169 IS - 4 U1 - http://www.ncbi.nlm.nih.gov/pubmed/25716342?dopt=Abstract ER - TY - JOUR T1 - Recommendations for the use of long-term central venous catheter (CVC) in children with hemato-oncological disorders: management of CVC-related occlusion and CVC-related thrombosis. On behalf of the coagulation defects working group and the supportive the JF - Ann Hematol Y1 - 2015 A1 - Giordano, Paola A1 - Saracco, Paola A1 - Grassi, Massimo A1 - Luciani, Matteo A1 - Banov, Laura A1 - Carraro, Francesca A1 - Crocoli, Alessandro A1 - Cesaro, Simone A1 - Zanazzo, Giulio Andrea A1 - Molinari, Angelo Claudio KW - Adult KW - Blood Coagulation Disorders KW - Catheter Obstruction KW - Catheterization, Central Venous KW - Central Venous Catheters KW - Child KW - Hematologic Neoplasms KW - Humans KW - Risk Factors KW - Thrombosis AB -

Central venous catheters (CVC), used for the management of children with hemato-oncological disorders, are burdened by a significant incidence of mechanical, infective, or thrombotic complications. These complications favor an increasing risk in prolongation of hospitalization, extra costs of care, and sometimes severe life-threatening events. No guidelines for the management of CVC-related occlusion and CVC-related thrombosis are available for children. To this aim, members of the coagulation defects working group and the supportive therapy working group of the Italian Association of Pediatric Hematology and Oncology (AIEOP) reviewed the pediatric and adult literature to propose the first recommendations for the management of CVC-related occlusion and CVC-related thrombosis in children with hemato-oncological disorders.

VL - 94 IS - 11 U1 - http://www.ncbi.nlm.nih.gov/pubmed/26300457?dopt=Abstract ER -