Blood Podcast: Season 1, Episode 38
In this week’s episode, we will examine the effects of protecting and regenerating Paneth cells and intestinal stem cells in acute-graft-versus-host-disease, learn more about how Plasmodium falciparum gametocytes develop in the bone marrow by invading erythroblasts, and look at a meta-analysis of direct oral anticoagulants for treating cancer patients with acute venous thromboembolism.
Plasmodium falciparum sexual parasites develop in human erythroblasts and affect erythropoiesis
Malaria gametocytes develop in the bone marrow, as only mature parasites circulate and can infect mosquitoes. In a Plenary Paper, the authors elegantly delineate novel aspects of the process of maturation of gametocytes, demonstrating that they infect erythroblasts in the bone marrow niche and delay their maturation to allow for full parasite development.
Impact of arginine therapy on mitochondrial function in children with sickle cell disease during vaso-occlusive pain
Arginine, the substrate for nitric oxide production, is deficient in patients with sickle cell vaso-occlusive crisis. Morris et al report improved markers of oxidant stress and mitochondrial stress in platelet-rich plasma from 12 patients treated with intravenous arginine, suggesting that arginine may offer a potential therapeutic intervention for sickle crisis.
Genomic and epigenomic insights into the origin, pathogenesis, and clinical behavior of mantle cell lymphoma subtypes
Mantle cell lymphoma (MCL) is characterized by 2 major molecular subtypes, conventional and leukemic nonnodal MCL. In this month’s CME article, Nadeu et al investigate the genomic and epigenomic landscape of MCL to elucidate its complex genetic structure and characterize alterations that help to distinguish MCL subtypes.
Glucagon-like peptide 2 for intestinal stem cell and Paneth cell repair during graft-versus-host disease in mice and humans
Acute graft-versus-host-disease (GVHD) is associated with decreased intestinal stem cells (ISCs) and Paneth cells (PCs) following allogeneic hematopoietic cell transplant. In mouse models, treatment with teduglutide, a glucagon-like peptide-2 agonist, improves regeneration of ISCs and PCs and decreases GVHD, providing support for clinical trials of teduglutide for prevention of GVHD.
Endogenous TCR promotes in vivo persistence of CD19-CAR-T cells compared to a CRISPR/Cas9-mediated TCR knockout CAR
Knockout of the endogenous T-cell receptor (TCR) offers the potential for HLA-mismatched “off-the-shelf” chimeric antigen receptor (CAR) T cells without risking GVHD. Stenger et al show that TCR-negative CAR T cells have strong antitumor activity without GVHD in mice. However, they have reduced persistence, increasing susceptibility to relapse.
