@article {10797, title = {Idiopathic neutropenia of infancy: Data from the Italian Neutropenia Registry.}, journal = {Am J Hematol}, volume = {94}, year = {2019}, month = {2019 Feb}, pages = {216-222}, abstract = {

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).

}, issn = {1096-8652}, doi = {10.1002/ajh.25353}, author = {Farruggia, Piero and Fioredda, Francesca and Puccio, Giuseppe and Onofrillo, Daniela and Russo, Giovanna and Barone, Angelica and Bonanomi, Sonia and Boscarol, Gianluca and Finocchi, Andrea and Ghilardi, Roberta and Giordano, Paola and Ladogana, Saverio and Lassandro, Giuseppe and Luti, Laura and Lanza, Tiziana and Mandaglio, Rosalba and Marra, Nicoletta and Martire, Baldassare and Mastrodicasa, Elena and Motta, Milena and Notarangelo, Lucia Dora and Pillon, Marta and Porretti, Laura and Serafinelli, Jessica and Trizzino, Angela and Tucci, Fabio and Veltroni, Marinella and Verzegnassi, Federico and Ramenghi, Ugo and Dufour, Carlo} } @article {10745, title = {Loss-of-function mutations in cause a new form of inherited thrombocytopenia.}, journal = {Blood}, volume = {133}, year = {2019}, month = {2019 Mar 21}, pages = {1346-1357}, abstract = {

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{\textquoteright} 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.

}, issn = {1528-0020}, doi = {10.1182/blood-2018-07-859496}, author = {Marconi, Caterina and Di Buduo, Christian A and LeVine, Kellie and Barozzi, Serena and Faleschini, Michela and Bozzi, Valeria and Palombo, Flavia and McKinstry, Spencer and Lassandro, Giuseppe and Giordano, Paola and Noris, Patrizia and Balduini, Carlo L and Savoia, Anna and Balduini, Alessandra and Pippucci, Tommaso and Seri, Marco and Katsanis, Nicholas and Pecci, Alessandro} } @article {10546, title = {Mutations of RUNX1 in families with inherited thrombocytopenia.}, journal = {Am J Hematol}, volume = {92}, year = {2017}, month = {2017 06}, pages = {E86-E88}, keywords = {Adult, Blood Platelets, Cell Size, Child, Child, Preschool, Core Binding Factor Alpha 2 Subunit, Female, Frameshift Mutation, Genes, Dominant, Heterozygote, Humans, Introns, Leukemia, Myeloid, Acute, Male, Middle Aged, Mutation, Missense, Protein Domains, RNA Splice Sites, Sequence Deletion, Thrombocythemia, Essential, Thrombopoietin, Transcriptional Activation, Young Adult}, issn = {1096-8652}, doi = {10.1002/ajh.24703}, author = {De Rocco, Daniela and Melazzini, Federica and Marconi, Caterina and Pecci, Alessandro and Bottega, Roberta and Gnan, Chiara and Palombo, Flavia and Giordano, Paola and Coccioli, Maria Susanna and Glembotsky, Ana C and Heller, Paula G and Seri, Marco and Savoia, Anna and Noris, Patrizia} } @article {7760, title = {Are all cases of paediatric essential thrombocythaemia really myeloproliferative neoplasms? Analysis of a large cohort.}, journal = {Br J Haematol}, volume = {169}, year = {2015}, month = {2015 May}, pages = {584-9}, abstract = {

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{\textperiodcentered}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{\textperiodcentered}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.

}, keywords = {Adolescent, Adult, Amino Acid Substitution, Child, Child, Preschool, Cohort Studies, Female, Hematologic Neoplasms, Humans, Infant, Janus Kinase 2, Male, Mutation, Missense, Neoplasm Proteins, Thrombocythemia, Essential}, issn = {1365-2141}, doi = {10.1111/bjh.13329}, author = {Randi, Maria L and Geranio, Giulia and Bertozzi, Irene and Micalizzi, Concetta and Ramenghi, Ugo and Tucci, Fabio and Notarangelo, Lucia D and Ladogana, Saverio and Menna, Giuseppe and Giordano, Paola and Consarino, Caterina and Farruggia, Piero and Zanazzo, Giulio A and Fiori, Giovanni M and Burnelli, Roberta and Russo, Giovanna and Jankovich, Momcilo and Peroni, Edoardo and Duner, Elena and Basso, Giuseppe and Fabris, Fabrizio and Putti, Maria C} } @article {8026, title = {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}, journal = {Ann Hematol}, volume = {94}, year = {2015}, month = {2015 Nov}, pages = {1765-76}, abstract = {

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.

}, keywords = {Adult, Blood Coagulation Disorders, Catheter Obstruction, Catheterization, Central Venous, Central Venous Catheters, Child, Hematologic Neoplasms, Humans, Risk Factors, Thrombosis}, issn = {1432-0584}, doi = {10.1007/s00277-015-2481-1}, author = {Giordano, Paola and Saracco, Paola and Grassi, Massimo and Luciani, Matteo and Banov, Laura and Carraro, Francesca and Crocoli, Alessandro and Cesaro, Simone and Zanazzo, Giulio Andrea and Molinari, Angelo Claudio} }