Hematopoiesis News Volume 4.46 | Nov 26 2013

Ligand-Independent FLT3 Activation Does Not Cooperate with MLL-AF4 to Immortalize/Transform Cord Blood CD34+ Cells
Investigators explored whether FLT3.TKD mutation or increased expression of FLT3.WT cooperates with MLL-AF4 to immortalize/transform cord blood-CD34+ hematopoietic stem/progenitor cells. [Leukemia] Abstract

Blood Stem Cell Fate Regulation by Delta-1 Mediated Rewiring of IL-6 Paracrine Signaling
Scientists demonstrated that although Delta-1 (DL1) activates STAT3 signaling similarly to the gp130-activating cytokine IL-6, it has opposite effects on myeloid cell production. Mechanistically, these different outcomes are attributable to a DL1-mediated reduction in membrane bound IL-6R expression, converting progenitor cells from being directly IL-6 responsive, to requiring both IL-6 and the soluble IL-6R for activation. [Blood] Abstract

Differences between Healthy Hematopoietic Progenitors and Leukemia Cells with Respect to CD44 Mediated Rolling versus Adherence Behavior on Hyaluronic Acid Coated Surfaces
Researchers quantitatively assessed the interaction of hematopoietic progenitor cells derived from umbilical cord blood, mobilized peripheral blood (mPB) and bone marrow (BM) from healthy donors, as well as primary leukemia blasts from PB and BM of patients with acute myeloid leukemia with hyaluronic acid. [Biomaterials] Abstract

Cell-Intrinsic In Vivo Requirement for the E47-p21 Pathway in Long-Term Hematopoietic Stem Cells
Scientists showed a direct genetic link between the transcription factor E47 and the major cell cycle regulator p21 in controlling long-term hematopoietic stem cell integrity in vivo under repopulation stress. [J Immunol] Abstract

Evaluation of Engraftment and Immunological Tolerance after Reduced Intensity Conditioning in a Rhesus Hematopoietic Stem Cell Gene Therapy Model
Scientists evaluated reduced intensity conditioning transplantation with 4Gy total body irradiation in two rhesus macaques that received equal parts of CD34⁺ cells transduced with green fluorescent protein-expressing lentiviral vector and empty vector not expressing transgenes. [Gene Ther] Abstract

Changes in the Frequencies of Human Hematopoietic Stem and Progenitor Cells with Age and Site
Investigators enumerated CD45hi/CD34+ and CD45hi/CD133+ human hematopoietic stem cells and granulocyte-monocyte colony forming progenitor cells in blood and trochanteric and femoral bone marrow in 233 individuals. Stem cell frequencies were determined by multi-parameter flow cytometry employing an internal control to determine the intrinsic variance of the assays. [Exp Hematol] Abstract

CLINICAL RESEARCH

Diverse T Cell Responses Characterize the Different Manifestations of Cutaneous Graft-versus-Host Disease
Graft-versus-host disease is a major complication of allogeneic hematopoietic stem cell transplantation (HCT) and can present in an acute (aGVHD), a chronic lichenoid (clGVHD) and a chronic sclerotic form (csGVHD). It is unclear whether similar or different pathomechanisms lead to these distinct clinical presentations. To address this issue, researchers collected lesional skin biopsies from aGVHD, clGVHD and csGVHD patients as well as serial non-lesional biopsies from HCT-recipients and subjected them to phenotypic and functional analyses. [Blood] Abstract

Analysis of Donor and Recipient ABO-Incompatibility and Antibody Associated Complications after Allogeneic Stem Cell Transplantation with Reduced Intensity Conditioning
A retrospective analysis of 310 patients that underwent allogeneic hematopoietic stem cell transplantation (ASCT) with reduced intensity condition between 1998 and 2011 was performed to investigate the frequency and clinical implications of anti-Red Blood Cell antibodies in passenger lymphocyte syndrome after minor ABO mismatch (mm), persistent or reoccurring recipient type ABO antibodies after major ABO mm ASCT and autoimmune hemolytic anemia. [Biol Blood Marrow Transplant] Abstract

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OmniBio Announces Notice of Allowance for New Use Patent
OmniBio Pharmaceutical, Inc. announced that it has received a Notice of Allowance from the Canadian Patent Office for the use of alpha-1 antitrypsin in reducing the risk of a non-organ transplant rejection, reducing the risk of developing graft versus host disease (GvHD) and for treating GvHD in patients who have received a cornea, bone marrow, stem cell or pancreatic islet cell transplant. [OmniBio Pharmaceutical, Inc.]
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