Blood
Articles in this Issue
The hepatic FGFR-ERK-HRG axis regulates heparin-induced thrombocytopenia with thrombosis
Heparin-induced thrombocytopenia (HIT) is a life-threatening prothrombotic disorder with substantial clinical mortality, characterized by pathologic antibody formation against platelet factor 4 (PF4)-...
HOW I TREAT BLEEDING IN WOMEN AND GIRLS WITH HEMOPHILIA/ HEMOPHILIA CARRIERS
Historically the impact of hemophilia for female carriers was believed to be restricted to their male offspring. Recent studies have highlighted the increased bleeding experienced by many hemophilia c...
Measurable Residual Disease-Dependent Unfavorable Outcomes in Pediatric PAX5-Rearranged B-Acute Lymphoblastic Leukemia
PAX5-altered acute lymphoblastic leukemia (PAX5-alt ALL) is a recently recognized molecular subtype of B-ALL characterized by a distinct transcriptional signature and frequent PAX5 fusions (PAX5-r). W...
FERMT3 alternative splicing enhances kindlin-3 membrane recruitment for neutrophil adhesion during stress myelopoiesis
Leukocyte Adhesion Deficiency syndrome type III (LAD-III) is characterized by recurrent infections and is caused by FERMT3 gene mutations. FERMT3 encodes two isoforms, a standard kindlin-3 and a longe...
Risk of recurrence in patients with provoked venous thromboembolism: a prospective cohort study
Venous thromboembolism (VTE) provoked by transient risk factors is generally considered low risk, supporting short-term anticoagulation. However, this paradigm is based on heterogeneous definitions of...
How I treat autoimmune neutropenia in adults
Autoimmune neutropenia (AiN) in adults is rare when compared to children. It occurs predominantly in female patients and in individuals with other autoimmune conditions. Anti‑neutrophil antibodies are...
Expansion of functional human long-term HSCs through restraining excessive cell cycle activation
Ex vivo expansion of human hematopoietic stem cells (HSCs) holds promise for overcoming their limited availability, a major barrier to broader clinical application. Although recent advances in culture...
A quantitative definition of the clinical manifestations of GATA2 deficiency in adults
Germline GATA2 deficiency is a pleiotropic condition 1-8 characterized by numerous phenotypes, including monocytopenia, immunodeficiency, microbial susceptibilities, and high rates of myeloid malignan...
Talquetamab in patients with relapsed/refractory multiple myeloma: 3-year follow-up of the phase 1/2 MonumenTAL-1 study
Talquetamab is the first and only approved bispecific antibody targeting G protein-coupled receptor class C group 5 member D (GPRC5D) for treatment of relapsed/refractory multiple myeloma based on res...
Recipient Endothelial IRF1 mediates IFNγ-driven tissue tolerance in mouse models of acute Graft-versus-Host Disease.
Recipient endothelial cells (ECs) actively respond to inflammation during allogeneic hematopoietic cell transplant (allo-HCT), yet mechanisms by which ECs influence acute graft-versus-host-disease (GV...
Boosting anti-leukemia cytotoxicity of CD4 and CD8 T cells through combined inhibition of MEK and HDAC
Acute myeloid leukemia (AML) is an aggressive blood cancer with a 5-year overall survival rate of ~30%. Although immunotherapies engaging T cells demonstrate remarkable success in treating many solid...
Functional restoration of immune defects in STAT1 gain-of-function disease following stem cell gene editing
Germline gain-of-function (GOF) mutations in the signal transducer and activator of transcription 1 (STAT1) gene cause a dominantly inherited inborn error of immunity (IEI) characterized by chronic mu...
DRP1-mediated mitochondrial fragmentation is a druggable vulnerability in multiple myeloma
Mitochondrial dynamics is a key regulator of cellular homeostasis, orchestrating metabolic reprogramming that fuels tumor progression and treatment resistance. In multiple myeloma (MM), however, the f...
1F10, a λ Light Chain Amyloid-Specific Monoclonal Antibody for Targeted Therapy of AL Amyloidosis
Light chain (AL) amyloidosis is a fatal plasma cell dyscrasia characterized by the overproduction of misfolded l or k immunoglobulin light chains (LCs) produced by clonal plasma cells, which aggregate...
Clinical and Genomic Convergence of High-Risk CCUS and Lower-Risk Myelodysplastic Syndromes/Neoplasms
Clonal cytopenia of undetermined significance (CCUS) is defined by unexplained cytopenias with myeloid-associated somatic mutations not meeting diagnostic criteria for myelodysplastic syndromes/neopla...
Characteristics of Donor and Recipient Clonal Hematopoiesis in Nonmyeloablative Transplant for Sickle Cell Disease
Sickle cell disease (SCD) is an inherited hemoglobinopathy characterized by chronic hemolytic anemia, painful vaso-occlusive episodes, and end-organ damage. Cellular therapies, including allogeneic he...
A first-in-class RNA degrader reduces c-MYC expression and myeloma cell survival in preclinical models
The c-MYC (MYC) oncogene is a critical driver of multiple myeloma (MM), however, direct targeting of the MYC protein has proven challenging due to its intrinsic structural disorder. In this study, we...
Erythroblast-derived lipid mediators program neutrophil development and function
Granulopoiesis is a tightly regulated process encompassing the production, maturation, and release of neutrophils in the bone marrow, ensuring their optimal physiological contribution to host defence....
Prime editing enables drug-controllable T-cell therapies with clinical immunosuppression
Current cell and gene therapies lack clinically practical mechanisms to selectively promote or suppress therapeutic cells in vivo, a limitation that is particularly acute in patients requiring ongoing...
Human HSPCs clones balance stochastic diversification with cytokine-induced differentiation
Hematopoietic stem and progenitor cells (HSPCs) balance self-renewal with on-demand differentiation of blood lineages. Modern bone marrow atlases specify static transcriptional states, but not HSPC dy...
Lisocabtagene maraleucel combined with ibrutinib in R/R CLL or SLL: primary results from TRANSCEND CLL 004
Patients in the liso-cel plus ibrutinib cohort of the phase 1/2, open-label TRANSCEND CLL 004 study had relapsed/refractory chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) and rece...
CD4+ T cells orchestrate the immune response to ALK-positive T-cell lymphoma
Immunotherapy has revolutionized the treatment of solid cancers in recent years. However, T-cell lymphomas (T-NHLs) originate from immune cells themselves and are biologically heterogeneous, rendering...
OPTI-AML: Prospective Comparison of 28 vs.14 days of Venetoclax Induction with Azacitidine in Older Adults with AML
Azacitidine (Aza) plus venetoclax (Ven) is standard treatment for older/unfit patients with newly diagnosed (ND) acute myeloid leukemia (AML). The approved 28-day (D) Ven schedule is associated with p...
MRD dynamics predicts progression and reveals a vulnerable state for immunotherapy interception in multiple myeloma
The clinical significance of one or two measurable residual disease (MRD) assessments is established in multiple myeloma (MM). However, how to stratify patients according to ≥3 MRD assessments remains...
Factor V is an anticoagulant of the extrinsic pathway of coagulation and modifier of thrombin generation in hemophilia A
Factor V (FV) links procoagulant amplification to anticoagulant feedback, but how FV limits tissue factor-initiated coagulation are not fully defined. We hypothesized that procofactor FV downregulates...