LABORATORY RESEARCH Cholesterol Efflux in Megakaryocyte Progenitors Suppresses Platelet Production and Thrombocytosis Investigators showed that transplantation of bone marrow deficient in ABCG4, a transporter of unknown function, into Ldlr-/- mice resulted in thrombocytosis, accelerated thrombosis and atherosclerosis. [Nat Med] Abstract Adhesion to Osteopontin in the Bone Marrow Niche Regulates Lymphoblastic Leukemia Cell Dormancy Researchers showed that osteopontin (OPN), an extracellular matrix molecule secreted by osteoblasts, can function to anchor leukemic blasts in anatomic locations supporting tumor dormancy. They demonstrated that acute lymphoblastic leukemia cells specifically adhere to OPN in vitro and secrete OPN when localized to the endosteal niche in vivo. [Blood] Abstract | Press Release Murine Natural Killer Cell Licensing and Regulation by T Regulatory Cells in Viral Responses Natural killer (NK) cells show differential functionality based on their capability of binding to self-MHC consistent with licensing. Investigators showed in vivo confirmation of the physiologic effects of licensing with differential effects of NK subsets on anti-murine cytomegalovirus responses after syngeneic hematopoietic stem cell transplantation or regulatory T-cell depletion. [Proc Natl Acad Sci USA] Abstract Autoantigen Can Promote Progression to a More Aggressive TCL1 Leukemia by Selecting Variants with Enhanced B-Cell Receptor Signaling (Auto)antigen engagement by the B-cell receptor and possibly the sites where this occurs influence the outcome of chronic lymphocytic leukemia. To test if selection for autoreactivity leads to increased aggressiveness and if this selection plays out equally in primary and secondary tissues, researchers used T-cell leukemia (TCL)1 cells reactive with the autoantigen phosphatidylcholine. [Proc Natl Acad Sci USA] Full Article Genomic Editing of the HIV-1 Coreceptor CCR5 in Adult Hematopoietic Stem and Progenitor Cells Using Zinc Finger Nucleases Given the low frequency of naturally occurring CCR5Δ32/Δ32 donors, scientists reasoned that engineered autologous CD34+ hematopoietic stem/progenitor cells could be used for AIDS therapy. [Mol Ther] Full Article Transplanted Murine Long-Term Repopulating Hematopoietic Cells Can Differentiate to Osteoblasts in the Marrow Stem Cell Niche Findings indicate that long-term repopulating hematopoietic stem cell (LTR-HSC) can give rise to progeny that differentiate to osteoblasts after bone marrow transplantation (BMT) suggesting a mechanism for prompt restoration of the osteoblastic HSC niche following BM injury, such as that induced by clinical BMT preparative regimens. [Mol Ther] Abstract CD19 CAR-Targeted T Cells Induce Long-Term Remission and B Cell Aplasia in an Immunocompetent Mouse Model of B Cell Acute Lymphoblastic Leukemia Researchers developed murine CD19-specific chimeric antigen receptors (CARs) and an immunocompetent mouse model of B cell acute lymphoblastic leukemia (B-ALL) that recapitulates the disease at genetic, cellular, and pathologic levels. Mouse T cells transduced with an all-murine CD3ζ/CD28-based CAR that is equivalent to the one being used in their clinical trials, eradicate B-ALL in mice and mediate long-term B cell aplasias. [PLoS One] Full Article In Vivo Expansion of Co-Transplanted T Cells Impacts on Tumor Re-Initiating Activity of Human Acute Myeloid Leukemia in NSG Mice The authors reported that in the NSG xenotransplantation assay, the large majority of mononucleated cells from patients with acute myeloid leukemia fail to establish a reproducible myeloid engraftment despite high donor chimerism. [PLoS One] Full Article CLINICAL RESEARCH Dose-Adjusted EPOCH-Rituximab Therapy in Primary Mediastinal B-Cell Lymphoma Primary mediastinal B-cell lymphoma is a distinct subtype of diffuse large-B-cell lymphoma that is closely related to nodular sclerosing Hodgkin's lymphoma. Researchers aimed to develop a strategy that improves the rate of cure and obviates the need for radiotherapy. [N Engl J Med] Abstract | Press Release Newly Diagnosed Adult AML and MPAL Patients Frequently Show Clonal Residual Hematopoiesis Researchers investigated the clonal vs. reactive nature of residual maturing BM cells in 59 newly-diagnosed adult acute myeloid leukemia (AML) and mixed phenotype acute leukemia (MPAL) patients as assessed by interphase fluorescence in situ hybridization analysis of AML and myelodysplastic syndrome-associated cytogenetic alterations and/or the pattern of chromosome X inactivation, in females. [Leukemia] Abstract |