Table of Contents
Hematopoietic cell fate decisions are regulated primarily by transcription factors that activate or repress lineage-specific gene expression programs.1 The transcription factors GATA-1/2 and Pu.1 are critical regulators of erythroid and myeloid cell differentiation. In this issue of Blood, Feng et al demonstrate that the histone methyltransferase disruptor of telomeric silencing (Dot1L), which catalyzes the methylation of histone H3 at lysine residue 79 (H3K79), is required for the proper activation of GATA-2 and for the repression of Pu.1 during erythropoiesis.2 Disruption of Dot1L activity in mice leads to early embryonic lethality in part due to a decrease in the expansion of erythroid progenitor cells and a defect in angiogenesis.
In this issue of Blood, Kantarjian and colleagues analyze the outcome of intensive, cytarabine-based induction chemotherapy in the management of elderly patients with newly diagnosed AML treated over an 18-year period, and challenge whether standard, available therapy should ever be offered to a vulnerable population of patients with both adverse clinical- and disease-related characteristics.1
Genetically targeted T lymphocytes are emerging as powerful antitumor agents. Their rapid generation, made possible by robust and clinically applicable gene transfer technologies, provides a novel means to circumvent immune tolerance and generate tumor-reactive T cells on demand. Thus, patient peripheral blood T cells can be readily redirected toward any chosen antigen, including tumor antigens which are for the most part “self” antigens, and infused to promptly raise the number of tumor-reactive T cells without requiring active immunization and without the risk of deleterious alloreactivity (as may be the case after donor leukocyte infusion or non-T cell–depleted bone marrow transplantation).
In this issue of Blood, Bao et al report an increase in regulatory T-cell activity in patients with ITP treated with thrombopoietin receptor (TPO-R) agonists.1 This finding implies that TPO-R agonists may have an unexpected immune-regulatory activity. If this is indeed the case, the mechanism by which TPO-R agonists could perform such a function is currently unclear.
In allogeneic stem cell transplantation, unsorted donor T cells are dangerous things: too many and the recipient runs the risk of death from severe graft-versus-host disease (GVHD); not enough and the graft may fail, the disease recur, and opportunistic infection arise. Smarter, more specific donor T cells might be better, but how specific does specific need to be to avoid trouble? In this issue of Blood, Melenhorst and colleagues allay anxieties about the use of virus-specific donor-derived T cells to prevent or treat viral reactivation and infection occurring after allogeneic transplantation.1 Their analysis of 153 transplant recipients given virus-specific donor-derived cells showed no de novo GVHD secondary to adoptive transfer and a rate of GVHD reactivation of only 6.5% with no reactivation greater than grade II in severity.
In this issue of Blood, Langer and colleagues demonstrate the inhibitory role of the complement system during neovascularization, which is mediated by complement-stimulated macrophages in both a mouse model of retinopathy of prematurity and in a Matrigel culture model.1
Complement-mediated inhibition of neovascularization reveals a point of convergence between innate immunity and angiogenesis
How I Treat
Clinical Trials and Observations
Intensive chemotherapy does not benefit most older patients (age 70 years or older) with acute myeloid leukemia
Prognosis of Binet stage A chronic lymphocytic leukemia patients: the strength of routine parameters
The B-cell tumor–associated antigen ROR1 can be targeted with T cells modified to express a ROR1-specific chimeric antigen receptor
Hematopoiesis and Stem Cells
ATP secreted by endothelial cells blocks CX3CL1-elicited natural killer cell chemotaxis and cytotoxicity via P2Y11 receptor activation
The JAK3-selective inhibitor PF-956980 reverses the resistance to cytotoxic agents induced by interleukin-4 treatment of chronic lymphocytic leukemia cells: potential for reversal of cytoprotection by the microenvironment
The PARP inhibitor olaparib induces significant killing of ATM-deficient lymphoid tumor cells in vitro and in vivo
Down syndrome and GATA1 mutations in transient abnormal myeloproliferative disorder: mutation classes correlate with progression to myeloid leukemia
Establishment of the first World Health Organization International Genetic Reference Panel for quantitation of BCR-ABL mRNA
Phagocytes, Granulocytes, and Myelopoiesis
Platelets and Thrombopoiesis
Transcription profiling in human platelets reveals LRRFIP1 as a novel protein regulating platelet function
Red Cells, Iron, and Erythropoiesis
Thrombosis and Hemostasis
Inhibition of the intrinsic coagulation pathway factor XI by antisense oligonucleotides: a novel antithrombotic strategy with lowered bleeding risk
Reduced-intensity versus conventional myeloablative conditioning allogeneic stem cell transplantation for patients with acute lymphoblastic leukemia: a retrospective study from the European Group for Blood and Marrow Transplantation
Allogeneic hematopoietic cell transplantation for hematologic malignancy: relative risks and benefits of double umbilical cord blood
Clinical Trials & Observations
Pericyte recruitment to EC-lined tubes stimulates vascular basement membrane assembly, including collagen type IV deposition, surrounding these tubes. Pericytes were allowed to recruit to EC-lined tubes in 3D collagen matrices for 3 days, and were then stained for collagen type IV in the absence of detergent permeabilization. Thus, only extracellular collagen type IV deposition was visualized. The cover image shows an intensity map of the degree of collagen type IV staining along an EC tube that was generated through analysis of a fluorescent image using MetaMorph software. The colors in the image are white, red, yellow, green, light blue, and purple, which in order represent the most intense to least intense staining. See the article by Stratman et al on page 4720.
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