ALBERT

Description: Article The integron integrases have evolved to perform recombination of single and double stranded DNA. Here the authors show that the ancestral pathway is still functional at double stranded sites, revealing the evolution towards the modern resolution pathway. Nature Communications doi: 10.1038/ncomms10937 Authors: Jose Antonio Escudero, Celine Loot, Vincent Parissi, Aleksandra Nivina, Christiane Bouchier, Didier Mazel

Description: WHO criteria defines platelet counts above 600×109/L as the threshold for essential thrombocythemia (ET) diagnosis. It has been argued that such threshold excludes a number of patients with ET with platelet counts below 600×109/L. Recently, a proposal for revision of the World Health Organization (WHO) diagnostic criteria for ET has been published, which includes the combination of histological bone marrow study and testing of JAK2 mutation. Design and methods: Retrospective analysis of 92 patients with ET diagnosis between 1989 and February 2008, isolating the subgroup of patients with platelet counts below 600×109/L. The aim of this study was to analyze the applicability of the 2008 WHO criteria in this subgroup. Results: Of the 92 patients, 30 patients did not fulfill the WHO criteria due to platelet counts

Description: L’étude des consommateurs et de la consommation est un des points d’entrée privilégiés pour comprendre les grandes transformations que le monde occidental a connues depuis le XVIIe siècle. L’évolution peut certes être analysée en termes de revenus et de prix, mais aussi par l’intermédiaire d’autres facteurs qui peuvent être déterminants : la différenciation des produits, le crédit, les habitudes sociales, la culture, la valeur symbolique des marchandises, le rôle des consommateurs, des acteurs non marchands dans la construction des marchés, les rythmes de développement ou de repli, l’importance des formes commerciales, depuis la boutique jusqu’aux structures de distribution qui ont permis l’élargissement de la consommation pour aboutir à la consommation de masse. Le présent ouvrage est le résultat d’un travail réalisé au sein du comité franco-espagnol d’histoire économique réunissant l’association française d’histoire économique et l’asociación española de historia económica. Il part du principe que les comparaisons entre la France et l’Espagne sont particulièrement pertinentes et à développer. Les chapitres analysent la consommation pré-industrielle ; le développement et la mesure du bien-être ; l’étude de la consommation par d’autres facteurs que les revenus et les prix et enfin, l’éclairage particulier lié à l’histoire de l’alimentation.

Description: Introduction: Morphology and cytogenetics are the basis for the study of MDS, however sometimes it is difficult to establish this diagnosis. The term ICUS was recently proposed (Mufti, 2005) for cases with persistent idiophatic cytopenia without evidence of dysplasia in the bone marrow (BM) smear, and normal cytogenetics. Aim: To evaluate the utility of FCI in detecting dysplasia when it is not evident by morphology. Patients: 24 patients with idiopathic cytopenia lasting for more than 6 months were evaluated for MDS using BM morphologic examination including iron stain, cytogenetics, FISH (5, 7, 8, 20q) and FCI. In 11 cases biopsy BM sections were examined. Other causes of cytopenia were previously excluded. Material and Methods: FCI in bone marrow samples. Data studied: In the myeloid lineage: abnormalities in granularity and CD45 distribution, abnormalities in the phenotypic pattern of myeloid development (CD16/CD11b/CD13), and the absence of CD10 expression on mature granulocytes. In the monocytic lineage: CD2 and CD56 expression. In the red cells: abnormalities in CD71 and glycophorin A distribution. In B-cells, detection of a low percentage of CD10+ B-cell precursors (less than 1% of bone marrow B-cells). In myeloblasts, identification of more than 〉5% CD34+ cells, and evaluation of aberrant expression of CD7 and TdT in these cells (positive expression was described when 〉10% of CD34+ cells were positive for any of these antigens). FCI data were suggestive of MDS when at least, 4 of the 10 parameters studied were abnormal, If aberrancies in CD34 were detected, only 3 criteria of abnormalities instead of 4 were needing Results: In all cases, morphology did not establish a definitive diagnosis of MDS, and karyotype and FISH were normal. FCI was highly suggestive of MDS in 14/24 cases. In 9 of 14 patients, their follow-up (1–36 months, median 10 months) confirmed the diagnosis of MDS; among these, 4 cases had hypocellular BM. In 3 of the 14 patients, BM biopsy supported the FCI diagnosis of MDS, but repeat specimens were not possible. One patient with suggestive FCI findings developed transfusion dependent anemia, mild thrombocytopenia, and multiple FCI abnormalities, but although a second BM aspirate was performed, the smear did not demonstrate MDS. Another patient with significant abnormalities by FCI had no evidence of MDS after 1 year of follow-up. The 10 patients whose FCI did not suggest MDS, were clinically stable at the time of writing with mild alterations in hematological parameters, and without evidence of overt MDS (follow-up: 6–40 m, median: 20m). Conclusions: With the number of cases studied, FCI showed more sensitivity in detecting early phases and/or low-risk MDS than morphology. FCI was also useful in detecting hypocellular MDS. Absence of dysplasia by FCI was associated with no evidence of MDS. Incorporation of FCI to the study of ICUS might distinguish early phases or low-risk MDS from other non-clonal ethyologies.

Description: Flow cytometry is a widely used method to study most of the hematologic malignancies. The utility of bone marrow immunophenotyping for the evaluation of patients with myelodisplastic syndrome (MDS) is currently being evaluated but most of these studies are based on the analysis of a large number of monoclonal antibodies. OBJECTIVE: To explore the potential contribution of flow cytometry to the diagnosis of MDS using a reduced panel of conjugated monoclonal antibodies (MoAb). PATIENTS AND METHODS: 45 bone marrow specimens from patients with a diagnosis of MDS based on morphologic and cytogenetic parameters (17 RA, 12 RARS, 5 MMCL, 9 RAEB, 2 RAEB-t), were analyzed by flow cytometry. In addition, 25 samples of bone marrow obtained from patients with cytopenias, but no diagnosis of MDS, were also studied. The panel of MoAb used was designed to identify abnormalities in the differentiation pathways of erithroid (CD71 FITC/Gly A PE/CD45 PC5) and myeloid lineage (CD 16 FITC/CD11b PE/CD13 PC5) as well as the presence of specific aberrant features in the CD34+ myeloid cell population (TdT FITC/CD7 PE/CD34 PC5). All samples were analized by two independet observers. To establish the diagnosis of MDS by flow cytometry, it was necessary to describe either immunophenotypic abnormalities in both myeloid and erithroid lineages or abnormalities in only one lineage plus description of more than 5% of CD34+ cells or abnormalities in one lineage plus description of aberrant features in the CD34+ population, regardless of its percentage. RESULTS: In 43 of the 45 samples analyzed, flow cytometric criteria of MDS were described. Only two cases (1 RARS with normal karyotype and 1 RA with complex cytogenetics) were considered normal according to the immunophenotypic criteria (95% sensivity). Regarding the cohort control, 4 samples had flow cytometric criteria of MDS; 11 samples showed isolated antigenic aberrancies in the erithroid differentiation and the 11 samples left were considered as normal. CONCLUSIONS: Flow cytometry may be a useful tool in the diagnosis of MDS, even analysing only two hemopoietic cell lineages. The reduced panel of MoAb described here can be widely used, is easy to be applied and shows a high sensitivity and a low cost. However, the finding of isolated immunophenotypic abnormalities in some patients without cytologic data of MDS seems to negatively influence the specificity of the technique. Nevertheless, those cases presenting an abnormal immunophenotype and normal morphology should be carefully monitored during their ulterior follow-up.

Description: Abstract 4825 Introduction: The majority of patients with classical Hodgkinxs Lymphoma (cHL) are cured with primary treatment. However, a significant proportion of patients will not achieve a complete response (CR) or relapse after completion of initial therapy and need to be rescued with high-dose chemotherapy and stem cell transplantation (SCT): autologous (aSCT) and/or alogeneic (Alo-SCT). The identification of clinical and biological characteristics of these patients at diagnosis is still a challenge and the most prognostic systems used to date fail to identify a proportion of patients with worse prognosis. The best understanding of the biology of cHL could help to identify these patients and different groups works in the use of biological marker as determinants of clinical outcome. Bcl2 over-expression has been described in cHL and seems to be an independent marker associated to bad prognosis in probably relation with alterations in apoptosis regulatory molecules. Objetive: To retrospectively analyze the frequency of Bcl2 protein over-expression in tissue biopsies of patients diagnosed with cHL, which required intensive treatment in our centre. Patients and Methods: We revised clinical data and samples at diagnosis of patients with cHL who received SCT (aSCT or/and Allo-SCT) due to partial remission, relapse or progression and we determined Bcl2 expression protein by immunohistochemistry. All patients received at least 2 lines of treatment previous to intensive treatment with SCT. We analyzed the expression of Bcl2 according to each patient histology: Nodular Sclerosis (NE), Mixed cellularity (MC), Lymphocyte-rich (LR), and Lymphocyte-depleted (LD). Results: Between September 1997 and May 2010, 39 patients with cHL required intensive treatment in our center: 32 aSCT and 7 Allo-SCT due to partial remission, refractory, relapse or progression after first line of treatment. Average age was 32 years (range: 18–64), males: 25/females 14. The characteristics of patients and remission status at transplant are described in table 1. We had available samples at diagnosis from 31 out of 39 patients (80%): 20 NE, 5 MC, 6 LR and we found over-expression of Bcl2 in 17/20 (85%) NE; 5/5(100%) MC and 2/6 LR (33%). Conclusions: Our results suggest that over-expression of Bcl2 is frequent in patients with cHL which needed intensive treatment after failure of the first line of therapy (particularly with NE and MC). Further studies are needed to confirm the worse prognosis of Bcl2 expression in cHL and if may be useful at diagnosis in association with other clinical parameters to identify patients with poor prognosis. Alo-SCT: Alogeneic stem cell transplant; aSCT: autologous stem cell transplant; CR: Complete Remission; F: female; LD: Lymphocyte-deplete; LR: Lymphocyte rich; M: male; MC: mixed cellularity Md: median; n: number; NE: nodular sclerosis; Nv: negative; P: positive; PR: Parcial remision R: range; RF: refractory Disclosures: No relevant conflicts of interest to declare.