Issue Archive

Pagano and colleagues provide new insight into outcomes for vaccinated patients with blood cancers in the Omicron variant era of the current COVID-19 pandemic. Based on registry data, the rate of mortality with breakthrough COVID-19 infection postvaccination is 9%. Multivariable analysis indicates that patients who have received monoclonal antibodies, alone or with antivirals, have better clinical outcomes. These and other data confirm that COVID-19 remains a threat to vulnerable patients and that both vaccination and treatment strategies are necessary as new variants emerge.

Natural killer (NK) cells reconstitute early after allogeneic stem cell transplants and are associated with protection against acute myeloid leukemia (AML) relapse. Wang and colleagues reveal that in patient samples, glycoprotein A repetitions predominant (GARP) molecules present on CD4⁺ regulatory T cells activate latent TGF-β1 to downregulate NK cell-effector functions in patients, enabling early AML relapse. The authors report that TGF-β1 inhibitors restore the antileukemia effector functions of NK cells in xenografts, potentially pointing to how NK cell-mediated control of AML can be increased in patients.

Melo-Cardenas and colleagues use a combination of mouse models, primary samples from patients with myeloproliferative neoplasms, and single-cell approaches to dissect how interleukin-13 (IL-13) and transforming growth factor-β (TGF-β) drive fibrosis and disease progression. The authors show that IL-13 promotes megakaryocyte growth and TGF-β surface expression in vivo, with reduction in IL-13 signaling-reducing fibrosis. Their data suggest a novel therapeutic target for patients with myelofibrosis.

Chronic immune thrombocytopenia (ITP) has complex pathophysiology. Using patient samples and murine models, Ni et al reveal that at least part of the prolonged therapeutic effect of the hypomethylating agent decitabine in ITP is via enhancement of oxidative metabolism and function of myeloid-derived suppressor cells (MDSC), improving T-cell homeostasis. This effect of decitabine is dependent on the restoration of liver kinase B1 (LKB1) expression in MDSC.

Javitt and colleagues report on a new 3D structure of von Willebrand factor showing that the previously unappreciated A1 domain is necessary for forming helical tubules matching those in Weibel-Palade bodies. This work provides a new understanding of A1 domain function in addition to its important roles following secretion.

Recombinant tissue-plasminogen activator (rtPA) is the mainstay of treatment of acute ischemic stroke, but a significant number of thrombi are resistant to lysis. van Moorsel et al report on initial results of a novel von Willebrand factor (VWF)-targeting PA, Microlyse, in murine models of stroke, demonstrating superiority over rtPA in platelet-rich thrombus-induced ischemia and equivalent results with fibrin-rich thrombi. Further studies are required to understand whether this enables advances in therapy for patients with acute thrombotic stroke.