Issue Archive

Voso et al review the current understanding of pathogenesis and treatment of t-MNs. They discuss the interplay of genomic variants, clonal hematopoiesis of indeterminate potential, aging, and other factors predisposing to acquisition of secondary mutations, especially in p53, in evolution to myeloid malignancy. They also describe new drugs and targeted agents that may improve the outcome on the terrible prognosis of t-MNs.

Di Giacomo and colleagues describe a heterogeneous group of acute leukemias associated with 14q32/BCL11B rearrangements. Depending on the nature of the rearrangements, the translocations are associated with immature M0 or M1 acute myeloid leukemia, mixed-phenotype acute leukemia, and early T-cell precursor acute lymphoblastic leukemia. Nevertheless, all display a specific gene expression signature that distinguishes these cases from other immature leukemias.

Imgruet et al investigated the role of the epigenetic modulator CUX1 in the pathogenesis of therapy-related myeloid neoplasms (t-MNs) in elegant in vitro and in vivo studies of mice with graded expression of CUX1. They demonstrate that CUX1 is critical for DNA repair and reduced CUX1 (as is commonly seen in t-MNs) leads to accumulation of DNA damage in cells that nevertheless continue to proliferate. In this model of t-MNs, restoring CUX1 reduces transformation, offering a possible entry point for preventing progression of clonal hematopoiesis to t-MNs.

PD-L1, the ligand for PD-1, has been demonstrated to be upregulated in neutrophils in sepsis. Wang et al report that neutrophil PD-L1 complexes with PI3 kinase to delay neutrophil apoptosis, enhancing neutrophil survival, and contributes to prolonging inflammation. PD-L1 inhibition is a candidate for reducing inflammation in the setting of inflammatory disease and sepsis.

Following a similar report on multiple myeloma, Ghione and colleagues report the expected observation that patients with non-Hodgkin lymphoma (NHL) receiving anti-B cell therapies have markedly reduced antibody responses to COVID-19 immunization. Although there is no information regarding T-cell immunity, this suggests that while vaccination is certainly still recommended for this population, patients should be strongly encouraged to maintain social distancing precautions and should be revaccinated after an appropriate interval from the end of their antilymphoma therapy.

Monoclonal antibodies such as daratumumab that target antigens that are also expressed on red blood cells impede blood group typing. The preferred approach to potential transfusion is to do prior extensive antigen typing of patients' red cells; however, this is not always possible. Ehrend et al describe a technique for absorbing the antibodies from serum to allow accurate red cell typing for transfusion.