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Marsafy S.E.L.,Laboratoire dhematologie biologique | Larghero J.,Cell therapy Unit and Clinical Investigation Center | Larghero J.,University Paris Diderot | Larghero J.,French Institute of Health and Medical Research
Current Stem Cell Research and Therapy | Year: 2015

Tumors grow in privileged microenvironment referred to as the cancer niche. This niche is composed of cancer cells and various components including mesenchymal stem cells (MSC), fibroblasts, network of microvasculature added to innate and primed immune cells. Additionally, it encloses other elements such as the extracellular matrix (ECM), cytokines, chemokines and growth factors. Crosstalk between cancer cells and different niche constituents is crucial for tumor growth and metastasis. Herein, we focus attention on the bidirectional relationship between MSC and cancer cells and its impact on tumor progression. Better comprehension of these events within the tumor niche might be valuable for developing effective anti-tumor therapeutic strategies. © 2015 Bentham Science Publishers. Source


Bissonnette J.,Service dHepatologie | Durand F.,Service dHepatologie | Durand F.,University Paris Diderot | de Raucourt E.,Laboratoire dhematologie biologique | And 8 more authors.
Journal of Clinical and Experimental Hepatology | Year: 2015

Vascular disorders of the liver frequently affect women of childbearing age. Pregnancy and the postpartum are prothrombotic states. Pregnancy seems to be a trigger for Budd-Chiari syndrome in patients with an underlying prothrombotic disorder. Whether pregnancy is a risk factor for other vascular liver disorders is unknown.In women with a known vascular liver disorder and a desire for pregnancy, stabilisation of the liver disease, including the use of a portal decompressive procedure when indicated, should be reached prior to conception. The presence of esophageal varices should be screened and adequate prophylaxis of bleeding applied in a manner similar to what is recommended for patients with cirrhosis. Most women likely benefit from anticoagulation during pregnancy and the postpartum. Labor and delivery are best managed by a multidisciplinary team with experience in this situation. Assisted vaginal delivery is the preferred mode of delivery. Although the risk of miscarriage and premature birth is heightened, current management of these diseases makes it very likely to see the birth of a live baby when pregnancy reaches 20 weeks of gestation. © 2015 INASL. Source


Awad F.,French Institute of Health and Medical Research | Georgin-Lavialle S.,French Institute of Health and Medical Research | Brignier A.,University of Paris Descartes | Derrieux C.,Laboratoire dhematologie biologique | And 5 more authors.
Orphanet Journal of Rare Diseases | Year: 2015

We report on a familial Mediterranean fever (FMF) patient homozygous for p.M694V in the MEFV gene who developed chronic myelomonocytic leukemia (CMML) leading to an uncontrolled and fatal inflammatory syndrome. Plasma levels of IL-6 and IL-18 were found to be very high, as compared to healthy controls and CMML-free FMF patients. Our study unveils the interplay between two different disorders involving the same target cells, suggesting that in myelodysplasia with inflammatory manifestations, mutations in genes causing autoinflammatory syndromes, like MEFV, can be present and thus could be sought. Early chemotherapy with interleukin inhibitors could be proposed in such unusual situations. © 2015 Awad et al. Source


Pasmant E.,University of Paris Descartes | Gilbert-Dussardier B.,Service de Genetique | Petit A.,University Pierre and Marie Curie | de Laval B.,University of Paris Descartes | And 17 more authors.
Oncogene | Year: 2015

Constitutional dominant loss-of-function mutations in the SPRED1 gene cause a rare phenotype referred as neurofibromatosis type 1 (NF1)-like syndrome or Legius syndrome, consisted of multiple café-au-lait macules, axillary freckling, learning disabilities and macrocephaly. SPRED1 is a negative regulator of the RAS MAPK pathway and can interact with neurofibromin, the NF1 gene product. Individuals with NF1 have a higher risk of haematological malignancies. SPRED1 is highly expressed in haematopoietic cells and negatively regulates haematopoiesis. SPRED1 seemed to be a good candidate for leukaemia predisposition or transformation. We performed SPRED1 mutation screening and expression status in 230 paediatric lymphoblastic and acute myeloblastic leukaemias (AMLs). We found a loss-of-function frameshift SPRED1 mutation in a patient with Legius syndrome. In this patient, the leukaemia blasts karyotype showed a SPRED1 loss of heterozygosity, confirming SPRED1 as a tumour suppressor. Our observation confirmed that acute leukaemias are rare complications of the Legius syndrome. Moreover, SPRED1 was significantly decreased at RNA and protein levels in the majority of AMLs at diagnosis compared with normal or paired complete remission bone marrows. SPRED1 decreased expression correlated with genetic features of AML. Our study reveals a new mechanism which contributes to deregulate RAS MAPK pathway in the vast majority of paediatric AMLs. Source


d'Audigier C.,Laboratoire dHematologie | Delassasseigne C.,HOpital Saint Antoine | Robert A.,HOpital Saint Antoine | Robert A.,University Pierre and Marie Curie | Eschwege V.,Laboratoire dhematologie biologique
International Journal of Laboratory Hematology | Year: 2016

Introduction: Pre-analytical phase is a critical step in the haemostasis laboratory cycle. Numerous variations affect tests results, and it is crucial to detect them in order to reject improper specimens before reporting test results. Comparing to prior results or requesting, a repeat sample can help in pre-analytical irregularity assessment. Methods: Each time a sample addressed to our laboratory displayed aberrant results or discordant with a prior report, another specimen was asked and both were analysed through calcium (Ca) level, prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen concentration, factor II, factor VII+X and factor V coagulant activity measurements. Among these, all the primary citrated samples from inpatients without anticoagulant treatment, displaying very low calcium level ('Ca 0' samples), were selected for this 2 years study. Results: A total of 17 samples could be identified. Ca level in their paired repeat samples was always >1.00 mmol/L. Coagulation testing for 'Ca 0' samples showed a significant prolongation of PT, APTT, TT and a significant decrease for fibrinogen concentration and factor V coagulant activity. Conclusion: We identified factor V coagulant activity, as the parameter with the most important variation in case of very low calcium level in presumed citrated sample tubes probably contaminated with EDTA. © 2016 John Wiley & Sons Ltd. Source

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