LABORATORY RESEARCH Growth Factor Independence 1 Antagonizes a p53-Induced DNA Damage Response Pathway in Lymphoblastic Leukemia Since oncogenic signaling activates a p53-dependent DNA damage response and apoptosis, leukemic cells must devise appropriate countermeasures. Researchers showed that growth factor independence 1 (Gfi1) can serve such a function because Gfi1 ablation exacerbates p53 responses and lowers the threshold for p53-induced cell death. [Cancer Cell] Abstract | Press Release Sustained PU.1 Levels Balance Cell-Cycle Regulators to Prevent Exhaustion of Adult Hematopoietic Stem Cells To provide a lifelong supply of blood cells, hematopoietic stem cells need to carefully balance both self-renewing cell divisions and quiescence. Although several regulators that control this mechanism have been identified, the authors demonstrated that the transcription factor PU.1 acts upstream of these regulators. [Mol Cell] Abstract miR-21 Mediates Hematopoietic Suppression in MDS by Activating TGF-β Signaling Scientists observed that SMAD7, a negative regulator of TGF-β receptor-I kinase, is markedly reduced in myelodysplastic syndromes (MDS), and leads to ineffective hematopoiesis by overactivation of TGF-β signaling. To determine the cause of SMAD7 reduction in MDS, they analyzed the 3’UTR of the gene and determined that it contains a highly conserved putative binding site for microRNA (miR)-21. [Blood] Abstract Transgene-Free iPSCs Generated from Small Volume Peripheral Blood Non-Mobilized CD34+ Cells Researchers report a method for deriving induced pluripotent stem cells (iPSCs) from peripheral blood hematopoietic stem cells (HSCs) using immunobead purification and 2-4 day culture to enrich CD34+ HSCs, followed by reprogramming with loxP-flanked polycistronic STEMCCA-loxP lentivector; or with Sendai vectors. [Blood] Abstract Hematopoietic Stem Cell and Progenitor Cell Mechanisms in Myelodysplastic Syndromes The authors transplanted purified human hematopoietic stem cells (HSCs) from myelodysplastic syndromes (MDS) samples into immunodeficient mice and show that HSCs are the disease-initiating cells in MDS. [Proc Natl Acad Sci USA] Abstract Chronic TLR Signaling Impairs the Long-Term Repopulating Potential of Hematopoietic Stem Cells of Wild Type but Not Id1 Deficient Mice To determine the effects of LPS treatment on hematopoietic stem cell function and to evaluate the significance of Id1 expression, the authors assessed the repopulating potential of wild type and Id1 deficient mice, which were subjected to a 30 day regimen of LPS treatment. [PLoS One] Full Article CLINICAL RESEARCH Treatment Reduction for Children and Young Adults with Low-Risk Acute Lymphoblastic Leukemia Defined by Minimal Residual Disease (UKALL 2003): A Randomized Controlled Trial Minimal residual disease (MRD) is the most sensitive and specific predictor of relapse risk in children with acute lymphoblastic leukemia during remission. Researchers assessed whether treatment intensity could be adjusted for children and young adults according to MRD risk stratification. [Lancet Oncol] Abstract H-Y Antigen-Binding B Cells Develop in Male Recipients of Female Hematopoietic Cells and Associate with Chronic Graft vs. Host Disease The authors previously showed that IgG allo-antibodies recognize Y chromosome-encoded proteins (H-Y) and a dominant H-Y epitope, DEAD box protein (DBY-2) detectable 6-12 months after transplant in male patients who receive grafts from female donors (F→M) in hematopoietic cell transplantation (HCT). Here they present FACS studies of peripheral blood mononuclear cells collected 6 months after transplant showing that 16 of 28 F→M HCT patients have circulating donor B cells that express B-cell receptor specific for DBY-2. [Proc Natl Acad Sci USA] Abstract | Press Release Infusion of Megakaryocytic Progenitor Products Generated from Cord Blood Hematopoietic Stem/Progenitor Cells: Results of the Phase I Study Megakaryocytic progenitor cells (MPs) were produced and characterized from cord blood mononuclear cells under a serum free medium with cytokines. Researchers investigated the feasibility of expansion and infusion of cord blood-derived MPs in 24 patients with advanced hematological malignancies. [PLoS One] Full Article |