Issue Archive

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 this issue of Blood, Zhang and colleagues demonstrate that targeting factor XI expression by antisense oligonucleotides prevents arterial and venous thrombosis in treated mice without increasing the risk of bleeding.¹ 

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