Issue Archive

Complementing the recently published Blood articles outlining the 2022 International Consensus Classifications for hematological malignancies (Vol. 140, Issue 11), this pair of Special Reports illustrates how molecular pathology can be applied to precision medicine. de Leval and colleagues summarize the potential of DNA sequencing of tumors and cell-free plasma, epigenetic profiling, and single-cell analyses to inform clinical decision-making about diagnosis, prognosis, and treatment for patients with lymphoid neoplasms. Similarly, Duncavage and colleagues cover genomic profiling for myeloid neoplasms and the acute leukemias, focusing principally on somatic changes but also with emphasis on the emerging importance of germline gene mutations in certain diseases. Both articles provide up-to-date references for how to apply genomic information to practice.

Complementing the recently published Blood articles outlining the 2022 International Consensus Classifications for hematological malignancies (Vol. 140, Issue 11), this pair of Special Reports illustrates how molecular pathology can be applied to precision medicine. de Leval and colleagues summarize the potential of DNA sequencing of tumors and cell-free plasma, epigenetic profiling, and single-cell analyses to inform clinical decision-making about diagnosis, prognosis, and treatment for patients with lymphoid neoplasms. Similarly, Duncavage and colleagues cover genomic profiling for myeloid neoplasms and the acute leukemias, focusing principally on somatic changes but also with emphasis on the emerging importance of germline gene mutations in certain diseases. Both articles provide up-to-date references for how to apply genomic information to practice.

Elsawy et al present the patient-reported outcomes after axicabtagene ciloleucel (axi-cel) administered as second-line therapy in large B-cell lymphoma compared to salvage chemotherapy followed by autologous stem cell transplantation (ASCT) in the ZUMA-7 trial. In clinical responders, treatment with axi-cel delivers better quality-of-life and an earlier return to baseline functioning compared to salvage chemotherapy followed by ASCT. The results imply that, in addition to improving progression-free survival, axi-cel is better tolerated than the previous standard.

Ex vivo ligand-mediated activation of Notch signaling can be used to expand hematopoietic stem cells and immature T cells. Wilkens and colleagues apply these principles in creating a new system for the manufacture of Notch1-activated CD4⁺ CAR-T cells with enhanced cytokine production, expansion, helper T-cell function, and anticancer activity.

Zhu et al report on a novel gene therapy approach to β-hemoglobinopathies that enhances the expression of the δ-globin chain of the minor adult hemoglobin, HbA2 (α2δ2). The authors demonstrate that functional Kruppel-like factor 1 (KLF1)-GATA1 fusion proteins significantly increase δ-globin expression and reduce sickling of erythroid cells derived from human sickle cell disease (SCD) CD34⁺ cells. In an SCD mouse model, after gene therapy and transplantation, HbA2 production increases, anemia improves, and SCD-related organ pathology is reduced.

The discoid shape of platelets has always intrigued hematologists. Kimmerlin et al explore the relationship between shape and function in α4A- and β1-tubulin double knockout mice, revealing that spherical platelets are dysfunctional. Despite normal activation and secretion of granules in vitro, under flow conditions in vivo mutant platelets show reduced adhesion, diminished thrombus formation, and increased bleeding.

Previous studies suggest that gut microbiome disruption induced by chemotherapy, dietary deficiencies, and/or antibiotics are associated with increased incidence of acute graft-versus-host disease (aGVHD) following hematopoietic stem cell transplantation (HSCT). In a murine model of antibiotic-induced gut microbiome disruption, Holmes and colleagues show that oral administration of galactooligosaccharides (GOS) as a prebiotic attenuates lethal aGVHD, highlighting the crosstalk between diet and gut microbiota. Their data encourage clinical trials of GOS prebiotic diets during HSCT.