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BLOOD COMMENTARIES

PLENARY PAPER

Fewer than 5% of people with chronic human T-cell leukemia virus type 1 (HTLV-1) infection develop adult T-cell leukemia/lymphoma (ATLL), and the interval between infection and leukemia diagnosis is typically decades. In this Plenary Paper, Rowan and colleagues map the emergence of clones bearing ATLL-associated genomic variants and leukemogenic mutations, revealing the kinetics of evolution of the malignant clone in ATLL and raising the prospect for development of predictive biomarkers of transformation.

PERSPECTIVE

Connors and Levy provide a Perspective on the coagulopathy observed in patients with severe COVID-19, highlighting its pathophysiology and relationship to inflammation and providing practical suggestions for the prevention and management of venous thrombosis in this setting.

CLINICAL TRIALS AND OBSERVATIONS

Ruppert and colleagues provide a comparison of 3 validated prognostic indices for patients with newly diagnosed diffuse large B-cell lymphoma, using data from 7 major trials and 2124 patients. They identified a shortcoming common to all: discrimination of patients with very poor prognosis.

HEMATOPOIESIS AND STEM CELLS

Loss of heterochromatin is postulated as a universal mechanism of aging across cell types. However, Keenan and colleagues revealed that murine hematopoiesis is remarkably tolerant of severe heterochromatin disruption, in part due to redundancy between 2 Suv39h enzymes in the protection of hematopoietic stem cells from accelerated aging.

MYELOID NEOPLASIA

Small nucleolar RNAs (snoRNAs) are noncoding RNAs that may play important roles in leukemogenesis. Using snoRNA-focused CRISPR-Cas9 knockout library screens, Pauli and colleagues revealed SNORD42A to be an essential modulator of ribosomal protein translation and acute myeloid leukemia cell survival and proliferation.

RED CELLS, IRON, AND ERYTHROPOIESIS

Utilizing a murine model of sickle cell disease (SCD), Park et al identified that SCD induces a disorganized and structurally abnormal vascular network in the bone marrow and dysfunctional vascular niche. These pathological changes are rapidly reversible with a regular transfusion regimen that could potentially be translated to human SCD patients.

THROMBOSIS AND HEMOSTASIS

Cines and colleagues describe how the neonatal immunoglobulin G (IgG) Fc receptor (FcRn) participates in the induction of tissue factor activity by IgG-containing immune complexes. Their cell line and in vivo model data suggest that inhibition of FcRn may reduce the prothrombotic phenotype of patients with disorders mediated by IgG-containing immune complexes, such as warm autoimmune hemolytic anemia.

TRANSPLANTATION

Wiskott-Aldrich syndrome (WAS) is an X-linked disease manifesting with thrombocytopenia, eczema, recurrent infections, autoimmune disease, and malignancy. Hematopoietic cell transplantation (HCT) is potentially curative. Burroughs and coauthors from the Primary Immune Deficiency Treatment Consortium (PIDTC) report excellent outcomes for WAS patients with modern allogeneic HCT and high-level myeloid engraftment.

LETTER TO BLOOD

Neelapu and colleagues report a post hoc subgroup analysis from the ZUMA-1 trial of chimeric antigen receptor T-cell therapy for relapsed or refractory diffuse large B cell lymphoma. In comparison with younger patients, those ≥65 years old have similar rates of complete response and durable response at 2 years, but higher rates of neurological toxicity.

BLOOD WORK

ERRATUM

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