Issue Archive

Hill and Seo use an illustrative clinical case to discuss issues of infection prophylaxis and therapy in patients prior to, during, and following chimeric antigen receptor T-cell therapy for B-cell malignancies.

Voorhees et al report results of a randomized trial of daratumumab added to standard frontline therapy with lenalidomide, bortezomib, and dexamethasone (RVd) in transplant-eligible patients with multiple myeloma. They demonstrated improved stringent complete response rates posttransplant that deepened over time.

FMS-like tyrosine kinase 3 (FLT3) somatic mutations are common driver mutations in acute leukemia. Yang et al used three-dimensional (3D) modeling to demonstrate that a subset of acute lymphoblastic leukemia harbors a small deletion in chromosome 13q12.2, leading to the overexpression of FLT3 in the absence a coding mutation. Lying 3’ of the FLT3 gene, the deletion alters the 3D interactions between a downstream enhancer and FLT3.

The authors investigated the role of SNAI1 in leukemogenesis, demonstrating that SNAI1 overexpression impairs differentiation and increases self-renewal and proliferation of myeloid progenitors.They demonstrated that the mechanism involves interaction with the histone demethylase KDM1A/LSD1, suggesting a potential role for LSD1 inhibitors in acute myeloid leukemia (AML) treatment.

Platelet binding to β-integrins is associated with bidirectional signaling. Inside-out signaling upon platelet activation facilitates platelet adhesion and aggregation; outside-in signaling amplifies platelet activation and thrombus extension. The authors demonstrated that modifying adaptor molecule binding to β-integrins can selectively inhibit thrombus extension without threatening primary hemostasis.

Matriptase-2 (MT2) suppresses hepcidin expression, a key regulator of iron metabolism. Though it is presumed to act by cleaving proteins in the BMP signaling pathway that upregulate hepcidin, the authors demonstrated that although MT2 does cleave key components in the hepcidin-induction pathway, its activity is dependent on substrate binding, and that proteolytic activity is dispensable for hepcidin regulation.

Haploinsufficiency of GATA2 caused by heterozygous loss-of-function mutations is associated with cytopenias and predisposition to myelodysplasia and AML with other variable extrahematopoietic manifestions, including lymphedema, pulmonary alveolar proteinosis, and hearing loss. The authors report on 2 siblings with the disorder whose father was asymptomatic because of an acquired missense mutation in the affected allele that was restricted to hematopoietic cells; surprisingly, he also had no extrahematopoietic complications.

With a median follow-up of 16.6 years, Lo and colleagues report excellent long-term outcomes with primary radiotherapy for limited-stage follicular lymphoma in this month’s CME article.