Incorporation and effect of arachidonic acid on the growth of human myeloma cell lines.

The objectives of this work are to investigate the incorporation of arachidonic acid (AA) in the human myeloma cell lines OPM2, U266 and IM9, and to assess the effect of AA and lipoxygenase products of AA on their growth. The kinetics of acylation of [3H]AA indicates that myeloma cells incorporate AA into their membrane phospholipids and triglycerides. PLA2-treatment and base hydrolysis experiments confirm that [3H]AA is incorporated unmodified in U266, IM9 and OPM2 phospholipids, and is linked by an ester bond. Prelabeling-chase experiments indicate no trafficking of labeled AA among the various phospholipid species. Addition of AA and lipoxygenase products of AA (leukotriene B4 and C4, lipoxin A4 and B4, 12- and 15-hydroxyeicosatetraenoic acid) have no effect on U266, IM9 and OPM2 proliferation assessed by [3H]thymidine incorporation into DNA. In conclusion, while human myeloma cells readily incorporate AA in their membrane phospholipids and triglycerides, AA and lipoxygenase products are not important modulators of their proliferation

Arachidonic acid and freshly isolated human bone marrow mononuclear cells.

Arachidonic acid (AA), a fatty acid found in the human bone marrow plasma, is the precursor of eicosanoids that modulate bone marrow haematopoiesis. To further our understanding of the role of AA in the bone marrow physiology, we have assessed its incorporation in human bone marrow mononuclear cells. Gas chromatography analysis indicates the presence of AA in their fatty acid composition. In bone marrow mononuclear cells, [3H]-AA is incorporated into triglycerides and is later delivered into phospholipids, a result not observed with blood mononuclear cells. Prelabelling-chase experiments indicate a trafficking of labelled AA from phosphatidylcholine to phosphatidylethanolamine. Stimulation of prelabelled bone marrow mononuclear cells with granulocyte-macrophage colony-stimulating factor (GM-CSF) results in the release of a part of the incorporated labelled AA. Finally, exogenous AA (up to 1 microM) has no significant effect on cell growth. In conclusion, human bone marrow mononuclear cells participate to the control of marrow AA concentrations by incorporating AA into phospholipids and triglycerides. In turn, bone marrow mononuclear cells can release AA in response to the potent haematopoietic growth factor GM-CSF

Front Line Treatment of Elderly Multiple Myeloma in the Era of Novel Agents

Melphalan combined with prednisone (MP) has long been the historical treatment of reference for a large proportion of elderly myeloma (MM) patients ineligible for autologous stem cell transplantation, and is still the backbone of new regimens that include the new era of novel agents. Melphalan–prednisone–thalidomide (MPT) and melphalan–prednisone–bortezomib (Velcade®, MPV), proved superior to MP, currently appear to be the treatments of choice for this population. In the near future melphalan–prednisone–lenalidomide (Revlimid®, MPR) will also provide a third therapeutic option (MPT, MPV, and MPR), in elderly multiple myeloma, eventually. These options could lead to more personalized treatment approaches, based on patient comorbidities, as the three novel agents have somewhat different toxicity profiles. Dexamethasone-based regimen is another option and questions regarding the relative efficacy of melphalan-based versus low-dose dexamethasone-based regimens will require randomized phase III trials. More intensive approaches with new drug combinations or with the incorporation of polyethylene glycolated (PEGylated) liposomal doxorubicin will also require additional studies. Additionally, the important issue of maintenance treatment needs to be further investigated. These new and emerging therapies offer multiple effective treatment options for MM patients and greatly enhanced treatment strategies for clinicians

Outcome of COVID-19 in Patients With Mantle Cell Lymphoma-Report From the European MCL Registry

Data on outcome of patients with mantle cell lymphoma (MCL) and COVID-19 infection are limited. The European MCL (EMCL) registry is a centralized registry of the EMCL network, collecting real-world information about treatments and disease courses. During the COVID-19 pandemic, additional data on MCL patients with COVID-19 infection were collected, aiming to identify risk factors for mortality from COVID-19. In our retrospective, multicenter, international study, we collected data from 63 MCL patients with a median age of 64 years (range, 44–84) in 9 countries with evidence of a COVID-19 infection between February 2020 and October 2021. The overall mortality rate was high (44.4%), especially in hospitalized patients (61%) and in patients with need for intensive care unit care (94%). Patients receiving rituximab had significantly poorer survival than patients not receiving rituximab (P = 0.04). Our data highlight the importance of prevention strategies and underline the need for effective vaccination in this vulnerable cohort

A system for creating virtual reality content from make-believe games

International audiencePretend play is a storytelling technique, naturally used from very young ages, which relies on object substitution to represent the characters of the imagined story. We propose a system which assists the storyteller by generating a virtualized story from a recorded dialogue performed with 3D printed figurines. We capture the gestures and facial expressions of the storyteller using Kinect cameras and IMU sensors and transfer them to their virtual counterparts in the story-world. As a proof-of-concept, we demonstrate our system with an improvised story involving a prince and a witch, which was successfully recorded and transferred into 3D animation

Identification of novel CD8+ T cell epitopes in human herpesvirus 6B U11 and U90

Human herpesvirus 6B (HHV6B) infects over 90% of the population, and normally establishes a latent infection, where episodes of reactivation are asymptomatic. However, in immunocompromised patients HHV6B reactivation is associated with high morbidity and mortality. Cellular immunotherapy has been utilised against other herpesvirus in immunocompromised settings. However, limited information on the immune response against HHV6B has hampered the development of immunotherapy for HHV6B-driven disease. In this study we have analysed the cellular immune response against four HHV6B antigens in a panel of 30 healthy donors. We show that the base-line level of T cell reactivity in peripheral blood is very low to undetectable. A short-term reactivation step enabled expansion of T cell responses, and all donors responded to at least 1 antigen, but more commonly 3 or 4. A hierarchy of immunogenicity was determined with antigens U90 and U54 being co-dominant, followed by U11 and U39. Putative CD8+ T cell epitopes were mapped to U90 and U11, predicted to be presented in the context of HLA-A1, A29, B39 and C6. T cells reactive against these novel epitopes were able to recognise virus-infected cells. Our data is supportive of the application and on-going development of T cell immunotherapy against HHV6B-driven disease in the immunocompromised host