1,721,541 research outputs found

    Issue Highlight 2015

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    This issue of Cytometry includes four papers dealing with the utility of flow cytometry (FC) immunophenotyping, together with fine-needle aspiration cytology (FNAC) or standard core biopsy in the diagnosis of extra-hematological tissues obtained from patients with different types of malignancies. These include thyroid lymphomas, breast implant- associated anaplastic large cell lymphomas, intracranial meningiomas, and brain tumor

    Issue highlights - May 2014

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    Paroxysmal nocturnal hemoglobinuria (PNH) is caused by somatic mutations in the PIG-A gene in hematopoietic stem cells and is characterized by the triad of intravascular hemolysis, severe acquired thrombophilia, and multiple cytopenias. The occurrence of cytopenias is thought to be an expression of bone marrow failure (BMF), and due to this consideration, a number of authors have recently investigated the presence of PNH clones in aplastic anemias (AA) and related disorders. Practical guidelines for the high sensitivity detection and monitoring of PNH clones by flow cytometry have been recently published in Cytometry B

    Issue Highlights-January 2013

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    To date, the diagnosis of acute myeloid leukemia (AML) with monocytic differentiation was limited by the lack of highly sensitive and specific monocytic markers. Over the last 2 decades, several immunophenotypic markers (lysozyme, elastase, UPA-R, GM-CSF-R, among others) were found to be preferentially expressed by cells belonging to the monocytic lineage, but unfortunately none of them allowed the easy recognition of the pure M5 FAB subvariety of AML.ILT3 is an immune inhibitory receptor expressed by myelomono- cytic cells and at high levels by tolerogenic dendritic cells, making it feasible to be incorporated into the initial diagnostic work-up and monitoring of patients with AML. However, the diagnostic usefulness of this pheno- typic marker for the recognition of the monocytic variant of AML needs to be validated in larger series of patients

    Toward standardization of Foxp3+ regulatory T‐cell measurement in clinical settings

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    Regulatory T-cells (T-regs) are a specialized subpopulation of T lymphocytes that act to suppress activation of other immune cells and to maintain immune system homeostasis, self tolerance, as well as to prevent excessive immune responses to foreign antigens. Over the last few years, evidence from both humans and animal models has accumulated that this cell subpopulation may play an important role in the pathogenesis of several diseases, suggesting that T-regs may be manipulated to treat those human diseases in the pathogenesis of which theyare implicated. Several reports provided evidence that autologous stem cell transplantation for autoimmune diseases may induce immunologic self-tolerance by reprogramming autoreactive T cells, thus restoring the immune regulatory network. The recent demonstration that T-regs could separate graft versus host disease from graft versus tumor reactivity represent another field in which the assessment of FoxP3þ T-regs play a role, and suggests that their immunosuppressive potential might be manipulated. Inhibition and depletion of T-reg inhibition represent another field of intervention in cancer immunotherapy. Furthermore, several studies also indicate that a defective T regulatory cell compartment can be modulated by B cell-targeted therapy or by antithymocyte globulin treatment, thus opening new scenarios in the treatment of various hematological malignancies as well as autoimmune diseases. To conclude, we believe that the article by Grant et al. furthers our insight on the characterization and enumeration of fresh and cryopreserved FoxP3-expressing T-regs in clinical samples; it should be kept in mind that the immunophenotypic profile of this cell subpopulation may vary significantly in cell culture over time, as a loss of FoxP3 expression after in vitro expansion of human CD4þ/CD25þ T-regs was recently documented. Such results illustrate the need for careful monitoring of T-regulatory cell populations in the setting of cellular therapeutic protocols where these may have an impact on disease outcome

    Sudan black B and peroxidase positivity in cultured lymphoid cells from patients with B-type chronic lymphocytic leukemia

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    In this paper authors have shown that cultured lymphoid cells from patients with B-cell type chronic lymphocytic leukemia may show positivity for peroxidase and sudan black B cytochemical reaction

    Towards standardization in immunophenotyping hematological malignancies. How can we improve the reproducibility and comparability of flow cytometric results?

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    Standardisation in immunophenotyping of hematological malignancies represents an important tool for the achievement of repiroducibility and compariability of results in multicenter trials. n order to get this goal, it is mandatory t make an effort in standardising techinical procedures, which can result in an improvenament in the concordance rates between different centres. Furthermore, the diagnostic and prognostic implications which can derive from the establisliment of consensus standards for the immunophenotyping ot leukemias could be relevant in many of these di sorder, particularly acute leukemias. In conclusion, in order to achieve a consensus on flow cytometry analysis of leukemic samples, both technological aspects, and reagents need to be standardised. It is likely that the establishment of consensus standards will lead to a considerable improvement in the comparability and reproducibility of the results within and between different centres, and will represent a basis for quality assurance and control programs. We hope that an algorithm for cell acquisition and analysis will be developed in the next few years, allowing an improvement in the concordance rates between different centres participating to mul ticenter trials

    Meeting report: Antisense oligonucleotides

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    The use of antisense oligonucleotides as a therapeutic tool in modulating gene expression represents a newly established strategy for treating diseases. Such oligomers may be designed to complement a region of a specific gene or messenger RNA. Using this approach, oligonucleotides can serve as a potential block of transcription or translation through sequence-specific hybridization with targeted genetic segments. In the Fourth Meeting of the Italian Society of Experimental Hematology "Discutiamone Insieme", authors reported the use of in vitro synthesized oligonucleotides to inhibit normal and chimeric gene expression of bcl-2 in normal and neoplastic cell lines, respectively, that carry the t(14;18) translocation. The roles of c-myb and B-myb in the control of the proliferation and differentiation of normal hematopoietic cell lines have been investigated by selective inhibition of the expression of specific transcripts. To get some insight into the correlation between proliferation and differentation in myeloid cells, some authors studied and reported the differentation potential of G1-arrested cells obtained by a specific oligodeoxynucleotide complementary to the 5' region of the c-myb mRNA. The use of anti-P53 antisense oligos in the modulation of the growth of normal and neoplastic bone marrow progenitors was presented and confirmed the pivotal role of this gene in cell cycle control. The role of abl gene expression in normal and chronic myelogenous leukemia (CML) cells is not yet completely understood. Selective inhibition of this proto-oncogene and of the abl-bcr oncogene have been achieved by using of c-abl sequence specific antisense oligonucleotides; this approach sheds new light on the function of this gene in CML. Furthermore, recent reports describe direct DNA interaction with oligonucleotides resulting in intermolecular triple helix (triplex) formation, or the use of a full antisense message in the inhibition of gene expression. The multidrug resistance (MDR1) gene was targeted by sequence specific oligonucleotides capable of forming a triplex helix with genomic DNA. The level of expression of the MDR1 gene was reduced in presence of these oligonucleotides, showing the usefulness of this new approach in the modulation of gene transcription. Finally, the use of an antisense messenger RNA (asRNA) strategy to study UL44 gene function (DNA polymerase accessory protein) in human cytomegalovirus (HCMV) was reported. Strong viral inhibition was been observed at various times after infection a sensitive cell line. The papers presented at this meeting, demonstrate the multiplicity of ways antisense RNA technology can be utilized for studying gene functions and offer a model for future specific gene therapy in normal, neoplastic and infective hematological diseases

    AIDS associated non Hodgkin’s lymphoma in Italy: intraveneous drug users versus homosexual men

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    Because of growing evidence that there are differences in the natural history of HTV infection in intravenous drug users (TVDU) and homosexual men, the clinicopathological features and response to treatment of AIDS-related nonHodgkin's lymphomas (NHL) were analyzed in 150 cases (96 IVDU and 31 homosexual men) by the Italian Cooperative Group on AIDS-related tumors. Twenty-three patients fell within other risk groups. The median age was 26 years for the IVDU and 38 for the homosexual men. Forty percent of patients in both of the risk groups manifested full-blown AIDS prior to development of the lymphoma. In both groups, most of the NHL were of high or intermediate type (TVDU 96%, homosexual men 86%). In high-grade NHL, Burkitt's type lymphoma was present in 40% of the homosexual men and in 29% of the IVDU (a non-significant difference), while an immunoblastic lymphoma was diagnosed in 46% of IVDU and 27% of homosexual men (non-significant). No oral localizations were observed, and one homosexual presented with a rectal lymphoma. Almost half of the patients (47%) received no antineoplastic treatment because of rapid disease progression or of diagnosis only at post-mortem. Intensive combination regimens administered in one-third of both IVDU and homosexual men (compared to CHOP or CHOP-like combinations) provided more CR (3/13 vs 3/24 in IVDU and 2/3 vs 1/7 in homosexuals), although the overall survivals with both the intensive and less intensive chemotherapy protocols remained similar. Overall, the median survival was 3.7 months for IVDU and 3.6 months for homosexual men. The most reliable predictors for survival were opportunistic infections at onset in IVDU. In both risk groups most patients died because of NHL progression. It is concluded that intravenous drug use by patients with AIDS-related NHL should not per se be considered a qualifying factor in the choice of type and intensity of antineoplastic treatment
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