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Widespread adoption of next-generation sequencing in myeloid malignancies is revealing the importance of inherited germ line predisposition disorders (GPDs). Feurstein and colleagues demonstrate that approximately 7% of patients with myelodysplastic dis-orders carry a pathogenic or likely pathogenic germ line variant associated with GPDs. This surprisingly high frequency has implications as to when germ line testing should be considered in this disease.


Genomic studies are changing how we understand many hematological diseases, but their quality is not always readily discernible. Dreval and colleagues suggest minimum reporting standards and address the important issue of how to adequately report on the quality of genomic experiments in contemporary hematology publishing using lymphoma studies as an example. This Blood Spotlight provides guidance for investigators planning, analyzing, and reporting sequencing studies.


Relapse and treatment-related mortality remain the biggest barriers to successful outcomes in pediatric hematopoietic stem cell transplant (HSCT). Pulsipher et al report on a prospective phase 2 multicenter trial investigating outcomes after αβ T cell/CD19-depleted hap-loidentical HSCT for 51 patients compared to a registry-based control group using other donor cell sources. The data are encouraging with 2-year disease-free survival of approximately 80% and low rates of treatment-related mortality and severe graft-versus-host disease when compared to more conventional grafts.


Syrykh et al report on the experience of the French Lymphopath network in the use of core needle biopsies (CNB), as compared with excisional lymph node biopsies, for the primary diagnosis of lymphoma. Their data indicate that CNB is reliable for most categories of lymphoma (92.3%) although lymph node excision leads to a higher rate of conclusive diagnoses (98.1%). CNB does increase the risk of erroneous or nondefinitive conclusions, and excisional biopsy may be preferable in some circumstances.

With any successful innovation comes some failure. By studying outcomes from a French registry, Di Blasi and colleagues highlight in this month’s CME article both the transformational nature of CAR T cells for relapsed aggressive B-cell lymphomas and the poor outcomes for patients progressing after this therapy. They report predictors and patterns of progression as well as outcomes with chemotherapy, targeted small molecules, and bispecific biologicals as salvage


Janssen and colleagues identify increased FLT3 signaling and associated MCL1 expression as hallmarks of high-risk acute myeloid leukemia (AML) with wild-type FLT3. They provide preclinical and preliminary clinical evidence that reducing FLT3 signaling through treatment with the FLT3 inhibitor gilteritinib reduces MCL1 expression and that the combination of gilteritinib and venetoclax is active in venetoclax-azacitidine resistant cell lines. These data suggest that prospective trials of this novel combination are warranted.


Some data suggest that macrophages, rather than stem cells, were the first blood cells to develop in primitive organisms. Nagahata and colleagues add to this notion by providing genetic evidence that phagocytes are the ancestral blood cell type during evolution. They identify the transcription factor C/EBPα as the driver of a conserved phagocytosis gene expression program and suggest that its repression eventually permitted the development of other blood cell lineages.


The alarmin S100A8/A9, also known as calprotectin, is secreted by activated myeloid cells and platelets. Colicchia et al report that S100A8/A9 plasma levels are increased in patients with COVID-19 and that sustained high levels are associated with worse clinical outcome.Mechanistically, S100A8/A9 induces the formation of procoagulant platelets through GPIbα supporting fibrin generation and immune-driven thrombosis.




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