Improvement of hemolytic anemia with GBT1118 is renoprotective in transgenic sickle mice
This article explores an important question: what are the impacts of novel sickle cell disease–modifying therapies, specifically voxelotor, on organ dysfunction? Ren and colleagues investigated voxelotor's murine analog GBT1118 and its effects on renal function in a transgenic sickle mouse model. The authors concluded that decreased hemolysis reduces exposure to cell-free hemoglobin and is therefore associated with the improvements they documented.
In vivo HSC transduction in rhesus macaques with an HDAd5/3+ vector targeting desmoglein 2 and transiently overexpressing cxcr4
Wang and colleagues present evidence that an adenovirus vector entering cells through desmoglein 2 and expressing cxcr4 can transduce in vivo hematopoietic stem cells at levels sufficient to correct sickle cell disease in a nonhuman primate model. This study is an important contribution to the field of in vivo transduction, which is key to the development of affordable, effective gene therapies.
Single-cell transcriptomics reveals the identity and regulators of human mast cell progenitors
Mast cells (MC) are a rare and understudied population, and they are important contributors to several pathological processes, including allergy and myeloproliferative neoplasms. In this study, Wu et al investigated the MC lineage in human hematopoietic tissue using a combination of single-cell RNA-seq, FACS analysis, and differentiation assays. The authors found that FceRI expression appears at the progenitor stage of MC differentiation in peripheral blood. Single-cell transcriptomics also revealed the expression pattern of prospective cytokine receptors that drive MC progenitor development, and follow-up culture assays showed that IL-33 induced FceRI downregulation.
Longitudinal study of glomerular hyperfiltration in adults with sickle cell anemia: a multicenter pooled analysis
Young patients with sickle cell anemia commonly suffer from glomerular hyperfiltration that precedes the development of overt kidney disease. In this study, Ataga et al enrolled a pooled multicenter cohort of patients with sickle cell anemia to estimate glomerular filtration rates using the 2009 creatinine-based CKD-EPI equation, which omitted race adjustment, and the 2021 CKD-EPI equation. The authors confirmed previous reports demonstrating high prevalence of hyperfiltration in young adults with sickle cell anemia. Somewhat surprisingly, however, they found similar results between the CKD-EPI 2009, without race adjustment, and the CKD-EPI 2021.
Idasanutlin plus cytarabine in relapsed or refractory acute myeloid leukemia: results of the MIRROS trial
In this article, Konopleva and colleagues present the results of a randomized phase 3 study of idasanutlin versus placebo in combination with intermediate dose cytarabine in patients with relapsed or refractory acute myeloid leukemia. Idasanutlin is an MDM2 inhibitor that has attracted interest with single-agent activity and promising activity in a single-arm combination study. Although the experimental arm showed a slight improvement in response rate primarily due to an increase in the number of CRi and CRp, the combination was terminated early and failed to meet the primary endpoint.
Code status transitions in patients with high-risk acute myeloid leukemia
Patients with high-risk acute myeloid leukemia (AML) experience elevated rates of hospitalizations and admissions to intensive care units. Nonetheless, end-of-life care and advanced care planning for these patients are limited. This study by Abrams and colleagues highlights the importance of investigating current code status practices in patients with high-risk AML. The results should encourage the hematologic community to implement interventions that enhance advance care planning and end-of-life experiences for these patients.
