Issue Archive

Atypical acute promyelocytic leukemias (aAPLs) arise because of rare fusions between 1 of the 3 retinoic acid receptor genes (alpha [RARA], beta, and gamma [RARG]) with various partners and are usually clinically resistant to all-trans retinoic acid (ATRA) therapy. In this Plenary Paper, Zhou and colleagues provide a molecular explanation for this resistance, revealing that all RARG and some RARA fusions involve 3 rather than 2 genes, with consequent loss of the ATRA-responsive transactivation domain. These discoveries simplify identification of aAPL cases where ineffective use of ATRA can be avoided soon after diagnosis.

Plasma exchange (PE) and immunosuppression (IS) have been mainstays of therapy for immune thrombocytopenic purpura (iTTP) for 30 years, with the addition of caplacizumab to the regimen, which has recently shown to accelerate and improve outcomes. Kühne et al used the Austrian Thrombotic Microangiopathy Registry to compare outcomes of caplacizumab and IS regimens with and without PE. The principal finding is that the PE-free regimen was safe, with key clinical outcomes not differing from PE-containing regimens, and hospitalizations were shorter. A definitive randomized trial is in progress, but in the interim, PE-free regimens for iTTP are appropriate in scenarios where PE is not immediately available.

Kaposi sarcoma herpesvirus (KSHV) is associated with a number of hematological diseases including primary effusion lymphoma, a plasmablastic form of multicentric Castleman disease, and KSHV-inflammatory cytokine syndrome. Lage et al profiled KSHV-associated diseases, finding that systemic inflammasome activation was common, but with patterns differing between the diseases. The inflammasome responses appeared to be dependent on monocyte activation by KSHV-infected cells.

Epigenetic dysregulation of gene expression is increasingly recognized in multiple myeloma (MM). Dupéré-Richer and colleagues combined clinical, genetic, and functional data to identify that the histone H3 at lysine 27 demethylase lysine demethylase 6A (KDM6A) directly regulated the immunogenicity of MM cells and compromised immune cell infiltration. Using a selective agent, the authors demonstrate that histone deacetylase 3 inhibition can partially compensate for the loss of KDM6A in MM cells, restoring immune recognition and providing a new potential avenue for treatment in selected MM subsets.

Red blood cells (RBCs) do more than carry hemoglobin and provide oxygen to tissues; abnormal RBCs are known to be prothrombogenic. Using murine and in vitro microfluidic models to control RBC and platelet counts, Jiang et al demonstrate a hemostatic effect of RBCs via platelet activation in settings of moderate thrombocytopenia and a platelet-independent effect via fibrin formation in severe pancytopenia. Furthermore, in high shear conditions, RBCs released adenosine 5’-diphosphate, contributing to the platelet activation and thrombosis seen in those with left ventricular assist devices. Collectively, these data stimulate further research into how RBCs support hemostasis in high-risk clinical circumstances.

As survival improves after hematopoietic stem cell transplantation (HSCT), young adults’ expectations for a normal life increasingly include a desire to have children. Using German Transplant Registry data, Sockel and colleagues found that although the birth rate is 6 times lower than that of the general population, the probability of a first live birth for women aged less than 40 after HSCT was 3.4%, with 72% of pregnancies occurring spontaneously. Key factors increasing the chance of motherhood include younger age, nonmalignant disease, and reduced-intensity conditioning. These encouraging findings remind physicians of the need to include discussion and implementation of fertility-preserving strategies in management.