Hematopoiesis News Volume 4.14 | Apr 16 2013

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 CCR5^Δ32/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

The Aging Hematopoietic Stem Cell Compartment
The authors summarize the phenotypes of aging hematopoietic stem cells (HSCs) and discuss how the cell-intrinsic and cell-extrinsic mechanisms of HSC aging might promote immunosenescence. [Nat Rev Immunol] Abstract

Is Hematopoietic Cell Transplantation Still a Valid Option for Mantle Cell Lymphoma in First Remission in the Chemoimmunotherapy-Era?
Modern chemoimmunotherapies have produced higher response rates and improved survival in mantle cell lymphoma (MCL); however, disease relapse remains a challenge. The availability of various post-remission maintenance or consolidation strategies have led some to question the role of upfront autologous hematopoietic cell transplantation consolidation for MCL in the chemoimmunotherapy-era. [Bone Marrow Transplant] Abstract

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BioLineRx Receives Regulatory Approval to Commence Phase II Clinical Trial for BL-8040, for Treatment of Leukemia
BioLineRx announced that it has received all necessary regulatory approvals in the US to commence a Phase IIa trial for BL-8040, for the treatment of acute myeloid leukemia. [BioLineRx] Press Release

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NEW Gordon-Merck Research Seminar: Cell Contact & Adhesion
June 1-2, 2013
Lucca (Barga), Italy

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Postdoctoral Position - Stem Cells and Cancer (Tsinghua University)

Cord Blood Laboratory Manager (Puget Sound Blood Center)

Postdoctoral Positions (Cancer Science Institute of Singapore)

Postdoctoral Positions - Cell Death Signaling & Cancer (Goethe Universität Frankfurt, Institute for Experimental Cancer Research in Pediatrics)

Postdoctoral Research Associate (Washington State University)

Postdoctoral Position - Hematopoietic Stem Cell Biology (Institut Pasteur, Labex Revive)

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