Giuseppe Palumbo

Publications (9)35.47 Total impact

• Article: Transplantation in the onco-hematology field: focus on the manipulation of αβ and γδ T cells.

  Nicola Daniele, Maria Cristina Scerpa, Maurizio Caniglia, Maria Ester Bernardo, Cecilia Rossi, Chiara Ciammetti, Giuseppe Palumbo, Franco Locatelli, Giancarlo Isacchi, Francesco Zinno
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  ABSTRACT: γ/δ T cells represent a subset of T cells expressing a T cell receptor (TCR) variant composed of gamma and delta chains. The γ/δ TCR is expressed by 2-10% of all T cells in human peripheral blood, whereas the majority of T cells express α/β TCRs. γ/δ T cells display a range of innate effector functions including rapid secretion of chemokines and cytokines, as well as target cell lysis. Recent interest has focused on the function of γ/δ T lymphocytes in allogeneic transplantation in the onco-hematology field. Several studies, in vitro and in vivo, suggest that γ/δ T lymphocytes are potential beneficial effector cells in the context of hematopoietic stem cell transplantation (HSCT). In addition, in this review, we discuss the depletion of α/β T lymphocytes in the graft for allogeneic transplantation. In fact, an efficient TCR α/β cell depletion potentially reduces the risk of GvHD. Furthermore, TCR α/β T cell depletion, especially with immunomagnetic negative selection, retains other potential beneficial effector cells in the graft, such as γ/δ T cells, NK cells, and stem cells. These "facilitating" cells might facilitate engraftment, exert GvL effects, and reduce the risk for infections.
  Pathology - Research and Practice 11/2011; 208(2):67-73. · 1.21 Impact Factor
• Article: Strategies to optimize the outcome of children given T-cell depleted HLA-haploidentical hematopoietic stem cell transplantation.

  Franco Locatelli, Luciana Vinti, Giuseppe Palumbo, Francesca Rossi, Alice Bertaina, Angela Mastronuzzi, Maria Ester Bernardo, Sergio Rutella, Paolo Dellabona, Giovanna Giorgiani, Alessandro Moretta, Lorenzo Moretta
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  ABSTRACT: The most advanced frontier of allogeneic hematopoietic stem cell transplantation (allo-HSCT) is represented by the use of an HLA-partially matched relative as donor. In this type of transplantation, donor-derived natural killer (NK) cells, which are alloreactive toward recipient cells, significantly contribute to the eradication of leukemia blasts. Alloreactive NK cells may also kill host dendritic cells and T lymphocytes, thus preventing graft-versus-host disease and graft rejection, respectively. Sophisticated strategies of adoptive infusion of T-cell lines/clones specific for the most life-threatening pathogens (namely cytomegalovirus, Epstein-Barr virus, Aspergillus and Adenovirus) have been envisaged, and successfully tested in a few pilot trials, to protect the recipient in the early post-transplantation period. In these patients, also ex-vivo expanded mesenchymal stromal cells have been shown to be beneficial for preventing graft failure. Novel and effective strategies aimed at further augmenting the graft-versus-leukemia effect and at optimizing prevention/treatment of opportunistic/viral infections are warranted.
  Best practice & research. Clinical haematology 09/2011; 24(3):339-49. · 3.13 Impact Factor
• Article: Early-onset monocyte-B-natural killer-dendritic cells' deficiency successfully treated with hematopoietic stem cell transplantation.

  Caterina Cancrini, Alessia Scarselli, Samantha Scaramuzza, Maria Chiriaco, Silvia Di Cesare, Gigliola Di Matteo, Maria Luisa Romiti, Paolo Palma, Lidia De Felice, Giuseppe Palumbo, Rita Maria Pinto, Rita De Vito, Luigi Racioppi, Susanna Livadiotti, Alain Fischer, Paolo Rossi, Maurizio Caniglia, Alessandro Aiuti
  The Journal of allergy and clinical immunology 08/2011; 128(4):897-900.e1. · 9.17 Impact Factor
• Article: Ex vivo expansion of mesenchymal stromal cells.

  Maria Ester Bernardo, Angela Maria Cometa, Daria Pagliara, Luciana Vinti, Francesca Rossi, Rosaria Cristantielli, Giuseppe Palumbo, Franco Locatelli
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  ABSTRACT: Mesenchymal stromal cells (MSCs) are adult multipotent cells that can be isolated from several human tissues. MSCs represent a novel and attractive tool in strategies of cellular therapy. For in vivo use, MSCs have to be ex vivo expanded in order to reach the numbers suitable for their clinical application. Despite being efficacious, the use of fetal calf serum for MSC ex vivo expansion for clinical purposes raises concerns related to immunization and transmission of zoonoses; the standardization of expansion methods, possibly devoid of animal components, such as those based on platelet lysate, are discussed in this paper. Moreover, this review focuses on the search of novel markers for the prospective identification/isolation of MSCs and on the potential risks connected with ex vivo expansion of MSCs, in particular that of their malignant transformation. Available tests to study the genetic stability of ex vivo expanded MSCs are also analyzed.
  Best practice & research. Clinical haematology 03/2011; 24(1):73-81. · 3.13 Impact Factor
• Article: Oxidative stress and defective platelet apoptosis in naïve patients with Kawasaki disease.

  Elisabetta Straface, Lucrezia Gambardella, Alessio Metere, Alessandra Marchesi, Giuseppe Palumbo, Elisabetta Cortis, Alberto Villani, Donatella Pietraforte, Marina Viora, Walter Malorni, Domenico Del Principe
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  ABSTRACT: Kawasaki disease (KD) is a rare and often undiagnosed disease, at least in the western countries. It is characterized by an inflammatory acute febrile vasculitis of medium sized arteries with a propensity to damage the coronary arteries. It normally occurs in the early childhood and the diagnosis is based on clinical symptoms. During the progression of the disease thrombocytosis is usually detected. This can exert a pathogenetic role in the cardiovascular complications occurring in KD. In the present work peripheral blood plasma and platelets from twelve naïve patients with KD were analyzed in order to detect possible pathogenetic determinants or progression markers. Morphological, biochemical and flow cytometrical methods have been used. With respect to age-matched healthy donors, we found an increase of platelet activation markers, i.e. degranulation, phosphatidylserine (PS) externalization and leukocyte-red cell-platelet aggregates. Some significant alterations that could represent suitable diagnostic determinants have also been detected in patient plasma: (i) decreased antioxidant power, (ii) decreased levels of asymmetric dymethylarginine (ADMA), a naturally occurring chemical interfering with the production of nitric oxide, and (iii) increased levels of soluble P-Selectin and soluble annexin V. Since PS externalizing platelets are known to exert a pro-coagulant activity, our data suggest the hypothesis that increased risk of vascular complications in KD could depend on platelet stimulation and defective apoptosis probably related to nitrosative stress.
  Biochemical and Biophysical Research Communications 02/2010; 392(3):426-30. · 2.48 Impact Factor
• Article: Mitochondria regulate platelet metamorphosis induced by opsonized zymosan A--activation and long-term commitment to cell death.

  Paola Matarrese, Elisabetta Straface, Giuseppe Palumbo, Maurizio Anselmi, Lucrezia Gambardella, Barbara Ascione, Domenico Del Principe, Walter Malorni
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  ABSTRACT: Changes in the mitochondrial membrane potential play a key role in determining cell fate. Mitochondria membrane hyperpolarization has been found to occur after cell activation, e.g. in lymphocytes, whereas depolarization is associated with apoptosis. The aim of this study was to investigate the effects of an immunological stimulus, i.e. opsonized zymosan A, on human platelet mitochondria by means of flow and static cytometry analyses as well as biochemical methods. We found that opsonized zymosan induced significant changes of platelet morphology at early time points (90 min). This was associated with increased production of reactive oxygen species, and, intriguingly, mitochondrial membrane hyperpolarization. At a later time point (24 h), opsonized zymosan was found to induce increased expression of CD47 adhesion molecule, platelet aggregation, mitochondrial membrane depolarization and phosphatidylserine externalization. Although these late events usually represent signs of apoptosis in nucleated cells, in opsonized zymosan-treated platelets they were not associated with membrane integrity loss, changes in Bcl-2 family protein expression or caspase activation. In addition, pre-treatment with low doses of the 'mitochondriotropic' protonophore carbonyl cyanide p-(trifluoro-methoxy)phenylhydrazone counteracted mitochondrial membrane potential alterations, production of reactive oxygen species and phosphatidylserine externalization induced by opsonized zymosan. Our data suggest that mitochondrial hyperpolarization represents a key event in platelet activation and remodeling under opsonized zymosan immunological stimulation, and opsonized zymosan immunological stimulation may represent a useful tool for understanding of the pathogenetic role of platelet alterations associated with vascular complications occurring in metabolic and autoimmune diseases.
  FEBS Journal 03/2009; 276(3):845-56. · 3.79 Impact Factor
• Article: Pretargeted antibody-guided radioimmunotherapy in a child affected by resistant anaplastic large cell lymphoma.

  Giuseppe Palumbo, Chiara M Grana, Francesca Cocca, Rita De Santis, Domenico Del Principe, Silvia M Baio, Riccardo Mei, Giovanni Paganelli
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  ABSTRACT: Anaplastic large cell lymphoma (ALCL) is characterized by preferential paracortical and intrasinusoidal lymph node involvement by large anaplastic tumor cells expressing the CD30 antigen. Up to 80% of pediatric patients with ALCL can be cured with multi-agent chemotherapeutic regimens. Patients resistant to chemotherapy or suffering from early relapse have a poor prognosis and a poor chance of survival. In these cases, the highly aggressive clinical course of ALCL, associated with systemic symptoms and extranodal involvement, has been treated with different approaches in various cooperative trials, including conventional chemotherapy and human stem cell transplantation (HSCT). However, the optimal treatment has not yet been defined, in particular in cases of relapse. More recently, radioimmunotherapy has been studied with encouraging results in cancer patients, including non-Hodgkin's lymphoma. Here we describe the case of a pediatric ALCL, relapsing after HSCT, treated with pretargeted antibody-guided radioimmunotherapy, obtaining a complete remission, with excellent quality of life over the past 10 months.
  European Journal Of Haematology 10/2007; 79(3):258-62. · 2.61 Impact Factor
• Article: Platelet-leukocyte interactions: platelets possess an antioxidant armamentarium.

  Domenico Del Principe, Gianluca Frega, Giuseppe Palumbo
  Thrombosis and Haemostasis 11/2003; 90(4):759-60. · 5.04 Impact Factor
• Article: Genotype-phenotype relationship in human ATP6i-dependent autosomal recessive osteopetrosis.

  Anna Taranta, Silvia Migliaccio, Irene Recchia, Maurizio Caniglia, Matteo Luciani, Giulio De Rossi, Carlo Dionisi-Vici, Rita M Pinto, Paola Francalanci, Renata Boldrini, Edoardo Lanino, Giorgio Dini, Giuseppe Morreale, Stuart H Ralston, Anna Villa, Paolo Vezzoni, Domenico Del Principe, Flaminia Cassiani, Giuseppe Palumbo, Anna Teti
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  ABSTRACT: Autosomal-recessive osteopetrosis is a severe genetic disease caused by osteoclast failure. Approximately 50% of the patients harbor mutations of the ATP6i gene, encoding for the osteoclast-specific a3 subunit of V-ATPase. We found inactivating ATP6i mutations in four patients, and three of these were novel. Patients shared macrocephaly, growth retardation and optic nerve alteration, osteosclerotic and endobone patterns, and high alkaline phosphatase and parathyroid hormone levels. Bone biopsies revealed primary spongiosa lined with active osteoblasts and high numbers of tartrate-resistant acid phosphatase (TRAP)-positive, a3 subunit-negative, morphologically unremarkable osteoclasts, some of which located in shallow Howship lacunae. Scarce hematopoietic cells and abundant fibrous tissue containing TRAP-positive putative osteoclast precursors were noted. In vitro osteoclasts were a3-negative, morphologically normal, with prominent clear zones and actin rings, and TRAP activity more elevated than in control patients. Podosomes, alphaVbeta3 receptor, c-Src, and PYK2 were unremarkable. Consistent with the finding in the bone biopsies, these cells excavated pits faintly stained with toluidine blue, indicating inefficient bone resorption. Bone marrow transplantation was successful in all patients, and posttransplant osteoclasts showed rescue of a3 subunit immunoreactivity.
  American Journal Of Pathology 02/2003; 162(1):57-68. · 4.89 Impact Factor