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Moalic-Allain V.,Laboratoire Of Genetique Moleculaire Et Dhistocompatibilite
Annales de Biologie Clinique | Year: 2014

The LuminexTM technology has become an important tool for HLA antibody screening and identification. This is the most sensitive technology to detect HLA antibodies for transplant patients and patients on awaiting list, and it has ushered a new strategy to determine HLA compatibility between donor and recipient. Moreover, the clinical relevance of all detected anti-HLA antibodies is not well understood, because this technique was shown to be prone to many artefacts or interferences, leading to a complicated interpretation for biologists and clinicians. Our objective in this article is to provide a careful consideration about this solid phase assay, and to focus attention on raised questions about technical performance and interpretation of the results.We should keep in mind that our results could change the clinical management of sensitized patients, their aptitude to receive a graft, and their follow-up. Source

De Braekeleer E.,University of Health Sciences | De Braekeleer E.,French Institute of Health and Medical Research | Douet-Guilbert N.,University of Health Sciences | Douet-Guilbert N.,French Institute of Health and Medical Research | And 10 more authors.
European Journal of Haematology | Year: 2011

Chromosomal rearrangements involving the ABL1 gene, leading to a BCR-ABL1 fusion gene, have been mainly associated with chronic myeloid leukemia and B-cell acute lymphoblastic leukemia (ALL). At present, six other genes have been shown to fuse to ABL1. The kinase domain of ABL1 is retained in all chimeric proteins that are also composed of the N-terminal part of the partner protein that often includes a coiled-coil or a helix-loop-helix domain. These latter domains allow oligomerization of the protein that is required for tyrosine kinase activation, cytoskeletal localization, and neoplastic transformation. Fusion genes that have a break in intron 1 or 2 (BCR-ABL1, ETV6-ABL1, ZMIZ1-ABL1, EML1-ABL1, and NUP214-ABL1) have transforming activity, although NUP214-ABL1 requires amplification to be efficient. The NUP214-ABL1 gene is the second most prevalent fusion gene involving ABL1 in malignant hemopathies, with a frequency of 5% in T-cell ALL. Both fusion genes (SFPQ-ABL1 and RCSD1-ABL1) characterized by a break in intron 4 of ABL1 are associated with B-cell ALL, as the chimeric proteins lacked the SH2 domain of ABL1. Screening for ABL1 chimeric genes could be performed in patients with ALL, more particularly in those with T-cell ALL because ABL1 modulates T-cell development and plays a role in cytoskeletal remodeling processes in T cells. © 2011 John Wiley & Sons A/S. Source

De Braekeleer M.,University of Health Sciences | De Braekeleer M.,French Institute of Health and Medical Research | De Braekeleer E.,University of Health Sciences | De Braekeleer E.,French Institute of Health and Medical Research | And 10 more authors.
Journal of Biomedicine and Biotechnology | Year: 2011

The development of the bacterial artificial chromosome (BAC) system was driven in part by the human genome project in order to construct genomic DNA libraries and physical maps for genomic sequencing. The availability of BAC clones has become a valuable tool for identifying cancer genes. We report here our experience in identifying genes located at breakpoints of chromosomal rearrangements and in defining the size and boundaries of deletions in hematological diseases. The methodology used in our laboratory consists of a three-step approach using conventional cytogenetics followed by FISH with commercial probes, then BAC clones. One limitation to the BAC system is that it can only accommodate inserts of up to 300kb. As a consequence, analyzing the extent of deletions requires a large amount of material. Array comparative genomic hybridization (array-CGH) using a BAC/PAC system can be an alternative. However, this technique has limitations also, and it cannot be used to identify candidate genes at breakpoints of chromosomal rearrangements such as translocations, insertions, and inversions. © 2011 Etienne De Braekeleer et al. Source

Moalic V.,Laboratoire Of Genetique Moleculaire Et Dhistocompatibilite
Pathologie Biologie | Year: 2013

Allogeneic haematopoietic stem cell transplantation is the choice treatment for many haematological malignancies. Granulocyte-colony-stimulating factor (G-CSF) has been widely used to mobilize stem cells into the peripheral blood from healthy siblings or volunteer unrelated donors. To a large extent, the use of mobilized peripheral blood haematopoietic stem cells has replaced marrow-derived stem cells as the preferred source of donor haematopoietic stem cells. Clinicians have been aware since the first clinical use, that administration of G-CSF, even in a single short course, could possibly be a risk for healthy donors either in short-term or as a delayed effect. The immediate side effects of G-CSF have been established for a long time, most of them are frequent but transient, self-limited and without long-term consequences. Questions have been raised about potential long-term adverse effects such as an elevated risk of haematological malignancies after G-CSF administration. More long-term safety data from registries are needed to adequately evaluate such a relationship. Our objective in this article is to provide an in-depth review of reported adverse events associated with the use of G-CSF in healthy donors and to focus attention on unanswered questions related to their long-term follow-up. © 2012 Elsevier Masson SAS. Source

Resnier P.,University of Western Brittany | Mottais A.,University of Western Brittany | Sibiril Y.,University of Western Brittany | Sibiril Y.,European University of Brittany | And 5 more authors.
Current Gene Therapy | Year: 2016

Numerous diseases affect the respiratory tract and the aerosol administration has been widely considered as an adapted and non-invasive method for local delivery. This pathway induces a lung concentration and thus also limits, systemic side effects. However, aerosol delivery of active pharmaceutical ingredients represents a real challenge, due to numerous obstacles such as the specific respiratory movement, the presence of mucus or surfactant, and the mucociliary clearance. Nanomedicines, such as liposomes, micelles or nanoparticles, offer the possibility to increase bioavailability and favor intracellular penetration of specific drugs into lung tissue. This review focuses on the description of aerosol formulations and cellular barriers including design, characteristics and progressive adaptation to airways anatomy. Then, aerosolized formulations currently clinically approved, or in clinical trial are summarized according to the encapsulated drug. In a final section, promising aerosol formulations in pre-clinical studies are detailed. © 2016 Bentham Science Publishers. Source

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