Project description:The goal of our study is to determine whether Atg16L1 deficiency leads to differences in the transcriptional profile of CD11c+ Dendritic Cells, ultimately leading to an increased inflammatory phenotype. CD11c+ cell sorted splenic DCs were isolated from 8 week old WT and Atg16L1 hypomorphic mice from spleens of allo-HSCT recipients on day 7 were placed directly into TRIzol LS (Invitrogen). mRNA was isolated, amplified, and hybridized to an Affymetrix GeneChip (MOE430A).
Project description:Longitudinally sampled peripheral blood samples of 9 CLL patients were subjected to single cell RNA sequencing before and at relapse after chemotherapy with fludarabine, cyclophosphamide and rituximab (FCR); allogeneic hematopoietic stem cell transplantation (RIC allo-HSCT); ibrutinib treatment, or before and after transformation to Richter's syndrome.
Project description:Transcriptome profiling of Acute Myeloid Leukemia samples. This dataset includes patients with diagnosis of de novo or secondary AML who experienced non-HLA loss disease relapse after allo-HCT, and for whom paired pre- and post-transplant viable leukemic samples were available.
Project description:Transcriptome profiling of Acute Myeloid Leukemia samples. This dataset includes patients with diagnosis of de novo or secondary AML who experienced non-HLA loss disease relapse after allo-HCT, and for whom paired pre- and post-transplant viable leukemic samples were available.
Project description:Transcriptome profiling of Acute Myeloid Leukemia samples. This dataset includes patients with diagnosis of de novo or secondary AML who experienced non-HLA loss disease relapse after allo-HCT, and for whom paired pre- and post-transplant viable leukemic samples were available.
Project description:Genotype profiling of Acute Myeloid Leukemia samples. This dataset includes patients with diagnosis of de novo or secondary AML who experienced non-HLA loss disease relapse after allo-HCT, and for whom paired pre- and post-transplant viable leukemic samples were available.
Project description:Main Objective: To evaluate the efficacy of vedolizumab when added to background aGvHD prophylaxis regimen compared to placebo and background aGvHD prophylaxis regimen on intestinal aGvHD-free survival by Day +180 in subjects who receive allo-HSCT as treatment for a hematologic malignancy or myeloproliferative disorder.
Primary end point(s): The primary endpoint is intestinal aGvHD-free survival by Day +180 after allo HSCT. Intestinal aGvHD is defined as Stage 1-4 intestinal involvement per Acute Graft versus-Host Disease Clinical Stage criteria.
Project description:Allogeneic hematopoietic stem cell transplantation is a potentially curative procedure for many malignant diseases. Donor T cells prevent disease recurrence via graft-versus-leukemia (GVL) effect. Donor T cells also contribute to graft-versus-host disease (GVHD), a debilitating and potentially fatal complication. Novel treatment strategies are needed which allow preservation of GVL effects without causing GVHD. Using murine models, we show that targeting IL-2-inducible T cell kinase (ITK) in donor T cells reduces GVHD while preserving GVL effects. Both CD8+ and CD4+ donor T cells from Itk-/- mice produce less inflammatory cytokines and show decrease migration to GVHD target organs such as the liver and small intestine, while maintaining GVL efficacy against primary B-cell acute lymphoblastic leukemia (B-ALL). Itk-/- T cells exhibit reduced expression of IRF4 and decreased JAK/STAT signaling activity, but upregulating expression of Eomesodermin (Eomes) and preserve cytotoxicity, necessary for GVL effect. Transcriptome analysis indicates that ITK signaling controls chemokine receptor expression during alloactivation, which in turn affects the ability of donor T cells to migrate to GVHD target organs. Our data suggest that inhibiting ITK could be a therapeutic strategy to reduce GVHD while preserving the beneficial GVL effects following allo-HSCT treatment.
