Issue Archive

Monogenic disorders leading to primary immunodeficiency have fascinated scientists and clinicians alike by their capacity to reveal the complexities of intracellular signaling pathways. Two articles in this issue of Blood by Abdollahpour et al and Nehme et al illustrate this point vividly, describing for the first time the clinical and immunologic phenotype associated with genetic mutations in STK4, manifested largely by a loss of T-cell naiveté.^1,2 

In this issue of Blood, Plesa et al demonstrate that human Foxp3⁺ regulatory T cells can be redirected using MHC class I–restricted T-cell receptors (TCRs), showing a surprising lack of correlation of TCR affinity and their suppressive potency.¹ 

In this issue of Blood, Yan et al¹  and Walz et al²  exploit mouse genetics to investigate the contribution of signal transducer and activator of transcription 5 (STAT5) to the abnormal in vivo growth of hematopoietic cells expressing JAK2^V617F or BCR-ABL. Eliminating STAT5 expression had dramatic effects in both contexts, and this new work and other recent studies support the therapeutic potential of targeting pathways regulated by this important signaling molecule in patients with myeloproliferative neoplasms (MPNs).

In this issue of Blood, Gerber et al use aldehyde dehydrogenase (ALDH) activity to further subdivide the CD34⁺CD38⁻ compartment in the bone marrow of acute myeloid leukemia (AML) patients. They identify a unique population with intermediate ALDH activity (ALDH^int) that contains leukemia stem cells (LSCs). Moreover, persistence of this population after therapy is a marker of clinically significant minimal residual disease.¹ 

In this issue of Blood, Pascale and colleagues show that biochemical resistance to aspirin in patients with essential thrombocythemia (ET) can be reversed by twice-daily dosing.¹ 

In a highly interesting, intricate, and novel paper in this issue of Blood, Fung and colleagues have extended their previous pioneering studies and now reveal that molecules such as ATP can promote platelet activation through the P2X1 receptor.¹ 

Bleeding in hemophilia is the result of factor VIII/IX deficiency with corresponding reduced thrombin production and enhanced fibrinolysis secondary to lower thrombin-activatable fibrinolysis inhibitor (TAFI) production. Factor replacement is the cornerstone of hemophilia treatment but is often not possible in developing countries.¹