Issue Archive

Cutaneous T-cell lymphomas (CTCLs) are a heterogeneous group of non-Hodgkin T-cell lymphomas of the skin. In this state-of-the-art review, Tensin et al discuss the impact of next-generation sequencing, which has allowed a better characterization of the genetic and epigenetic landscape that defines the spectrum of CTCL, permitting better definition of distinct subgroups of CTCL.

Patel et al report long-term outcomes of the phase 2 trial combining eltrombopag (EPAG) with immunosuppressive therapy (IST) for the treatment of newly diagnosed patients with severe aplastic anemia. As previously reported, adding EPAG improves responses in comparison to IST alone. However, there was no difference in the rate of relapse (29%) or the incidence of clonal evolution (15%), although events occur earlier in the EPAG group.

Aging is associated with impaired function and myeloid skewing of hematopoietic stem cells (HSCs) that has been attributed to age-associated inflammatory changes (“inflammaging”). Kovtonyuk et al demonstrate that the gut microbiome has a central role in this process by releasing microbial TLR4 and TLR8 ligands that increase marrow interleukin-1 (IL-1) production; IL-1 receptor knockout animals and germfree animals showed improved HSC function and decreased skewing. These data provide important insights into the process of HSC aging with potential important clinical implications.

Shen et al studied the stem cell regulatory protein SOX9 in the context of diffuse large B-cell lymphoma (DLBCL), demonstrating that SOX9 positivity correlates with advanced-stage disease and SOX9 silencing decreases lymphoma cell proliferation. Transcriptome analysis identified DHCR24, a critical enzyme for cholesterol biosynthesis, as the target of SOX9, and inhibition of cholesterol synthesis also decreased growth of DLBCL xenografts. This suggests that statins may synergize with chemotherapy in the treatment of DLBCL.

Mirroring recently reported observations in pediatric acute myeloid leukemia (AML), Taube et al report in a study of over 4700 adult patients that both monoallelic and biallelic in-frame mutations of the CEBPA bZIP domain confer good prognosis, whereas point mutations and non-in-frame mutations do not confer the same overall good prognosis.

Vertebrate lonesome kinase (VLK) is a widely expressed tyrosine kinase contained within platelet α -granules. Revollo and colleagues interrogated the role of VLK in platelet function through analysis of mice with a targeted VLK deletion in megakaryocytes and platelets. In the absence of VLK, platelets appeared normal but had in vitro and in vivo functional changes in platelet activation and thrombus formation, defining the first secreted protein kinase influencing normal platelet function.

Factor VIIa (FVIIa) initiates coagulation by binding to tissue factor but also binds the endothelial protein C receptor (EPCR), where it induces anti-inflammatory responses and protective barrier responses that reduce fluid extravasation. Das et al report that FVIIa binding to the EPCR leads to release of endothelial extracellular vesicles (EEVs) containing anti-inflammatory microRNAs that confer an anti-inflammatory phenotype on monocytes; further, uptake of EEVs confers cytoprotection. This may explain the long-term protective effects of FVIIa prophylaxis in hemophilia with inhibitors.

Three reports address the protection of the vulnerable population of patients with hematologic malignancies in the face of the ongoing COVID pandemic. The reports suggest that some patients who fail to mount a B-cell response to vaccine may nevertheless have protective T cell responses. As a group, these reports suggest that patients should continue to be immunized with additional doses to attempt to improve immune response but that they need to maintain the precautions recommended for the unvaccinated.

Three reports address the protection of the vulnerable population of patients with hematologic malignancies in the face of the ongoing COVID pandemic. The reports suggest that some patients who fail to mount a B-cell response to vaccine may nevertheless have protective T cell responses. As a group, these reports suggest that patients should continue to be immunized with additional doses to attempt to improve immune response but that they need to maintain the precautions recommended for the unvaccinated.

Three reports address the protection of the vulnerable population of patients with hematologic malignancies in the face of the ongoing COVID pandemic. The reports suggest that some patients who fail to mount a B-cell response to vaccine may nevertheless have protective T cell responses. As a group, these reports suggest that patients should continue to be immunized with additional doses to attempt to improve immune response but that they need to maintain the precautions recommended for the unvaccinated.