Blood
Articles in this Issue
Antiphospholipid syndrome (APS) is a platelet factor 4 (PF4)-centric immunothrombotic disorder
Antiphospholipid syndrome (APS) is an immunothrombotic disorder, frequently attributed to autoantibodies that bind β2-glycoprotein I (β2GPI). A study showed that the platelet-specific chemokine, plate...
TRANSFORM-1 Phase 3 study: Efficacy and safety of navitoclax plus ruxolitinib in patients with untreated myelofibrosis
The Phase 3 TRANSFORM-1 study (NCT04472598) evaluated ruxolitinib (RUX) in combination with navitoclax (NAV) or placebo (PBO) in Janus-kinase-inhibitor-naïve adults with intermediate-2 or high-risk my...
Menin-MLL inhibitors enhance JUND activity in MLLr leukemic cells contributing to tumorigenesis and therapy resistance
MLL-rearranged (MLLr) acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL) involve reciprocal translocations of the KMT2A (MLL1) gene with various translocation partner genes, which yields o...
One-stage Assay Factor VIII Activity Reflects AAV-Derived Factor VIII-Enhanced Thrombin Activation and Predicts Phenotype
Hemophilia A (HA) phenotype is predicted by factor VIII (FVIII) activity. Most HA adeno-associated virus (AAV) trials incorporate the B-domain-deleted FVIII-SQ variant and one-stage assay (OSA) FVIII...
Arterial iron regulates vasodilation during anemia via endothelial holo α-globin
Iron deficiency is a highly prevalent nutrient deficiency and the most common cause of anemia. Although iron deficiency exacerbates cardiovascular disease, the direct impact of iron deficiency on the...
NSD2 Degradation Remediates the Oncogenic Cistrome in t(4;14) Multiple Myeloma
The t(4;14) chromosomal translocation drives overexpression of the histone methyltransferase NSD2 and defines a high-risk segment of multiple myeloma (MM) patients. Herein, we report the discovery of...
FGF18 mediates fibroblast-leukemia crosstalk to promote acute myeloid leukemia progression
Non‑hematopoietic stromal cells are essential regulators of hematopoiesis; however, their contribution to leukemogenesis and immune dysfunction remains poorly defined. Here, we identified fibroblast‑d...
Direct and indirect regulation of fetal globin transcript by RNA-binding protein IGF2BP1
Despite extensive investigation, the molecular control of developmental hemoglobin expression remains incompletely elucidated. Hemoglobin switching is controlled by transcription factors, miRNAs, and...
Galectin-1 Fuels Monocyte Hyperinflammation and Represents a Novel Therapeutic Target in Myeloproliferative Neoplasms
Dysregulation of galectins and global protein glycosylation have been reported in various cancers, but their role in myeloproliferative neoplasms (MPNs) have remained incompletely understood. We perfo...
NG2-ITGA4 axis regulates Rho GTPases and leukemic aggressiveness in KMT2A-r B-ALL and is targetable with natalizumab
KMT2A-rearranged B-cell acute lymphoblastic leukemia (KMT2A-r B-ALL) is an aggressive subtype of leukemia, characterized by high relapse rates, therapy resistance, and poor prognosis. Although CD19-ta...
Combining Quizartinib with intensive chemotherapy in older patients with newly diagnosed AML: results of the UK NCRI AML18 Trial
We assessed the addition of the tyrosine kinase inhibitor Quizartinib, following intensive chemotherapy and as maintenance, in patients aged >60 years with AML or high-risk MDS, regardless of F...
Translational Regulation of Sf1 Integrates Alternative Splicing and Hematopoietic Stem Cell Fate
The transition of hematopoietic stem cells (HSCs) from quiescence to lineage commitment requires precise post-transcriptional control, yet the contribution of mRNA isoform regulation remains poorly de...
Niche-targeted therapy via YAP/TAZ activation enhances hematopoietic regeneration
The distinctive milieu of the bone marrow (BM), known as the BM niche, supports hematopoietic stem cells (HSCs) and serves as a foundation for hematopoietic regeneration. Myeloablative stress disrupts...
Expanded antigen-specific donor regulatory T cells for GVHD prevention
Minor histocompatibility antigen (mHAg)-specific alloreactive donor T cells cause graft vs. host disease (GVHD) in matched related donor allogeneic hematopoietic cell transplantation (HCT). In a phase...
Retinoic acid-driven expansion of CD16hiCD177+ neutrophils mediates steroid-resistant GI-GVHD
Steroid-resistant gastrointestinal graft-versus-host disease (SR-GI-GVHD) is a lethal complication of allogeneic hematopoietic stem cell transplantation with no clear therapeutic target. The role of n...
Aberrant splicing of MBD1 reshapes the epigenome to drive convergent myeloerythroid defects in MDS
Myelodysplastic neoplasms (MDS) feature hematopoietic deficits driven in part by transcript splicing abnormalities. Thus far, such disease-driving transcripts have been identified in association with...
Ibrutinib in early stage CLL: Genetic risk factors and treatment outcome in the GCLLSG CLL12 trial
Watch & wait is the standard of care in asymptomatic early-stage chronic lymphocytic leukemia (CLL). The CLL12 trial investigated ibrutinib versus placebo in early-stage patients with intermediate...
Targeting ACKR3/CXCR7 Enhances Platelet Anticoagulant Acylcarnitines and Modulates Procoagulant Function
Targeting ACKR3/CXCR7 regulates enzymatic generation of pro-thrombotic, while favoring anti-thrombotic lipids that inhibit platelets through AC-cAMP-PKA pathway in coordination with prostacyclin-IP re...
FAP-1 loss impairs megakaryocyte demarcation membrane system and platelet function with myelofibrosis-like features
Fas-associated phosphatase-1 (FAP-1), a nonreceptor protein tyrosine phosphatase, has been implicated in multiple signaling pathways, but its in vivo role remains unclear. Here, we show that FAP-1-def...
A Phase 2 trial of daratumumab monotherapy in newly diagnosed patients with cardiac stage IIIb AL amyloidosis
Treatment options for patients with immunoglobulin light chain (AL) amyloidosis and advanced cardiac involvement remain limited. The prospective, phase 2 EMN22 trial included previously untreated pati...
Anbalcabtagene autoleucel (PD-1 and TIGIT knockdown CD19 CAR-T) for relapsed/refractory large B-cell lymphoma (CRC01-01)
Anbalcabtagene autoleucel (Anbal-cel) is a CD19-directed CAR T-cell therapy incorporating dual PD-1 and TIGIT knockdown to enhance antitumor function and durability. We report the results of a Phase 1...
Anticoagulation with mechanistically distinct FXI/FXIa antibodies amrecibart (REGN9933A2) and cenvacibart (REGN7508Cat)
Thrombosis is a major contributor to global morbidity and mortality. Current standards of care target the extrinsic and/or common pathways of coagulation, effectively inhibiting thrombosis but also in...
Anti-fibrinolytic strategies improve liver regeneration in mice and reduce post-hepatectomy liver failure in patients
Pharmacological plasminogen reduction enhanced liver regeneration experimentally and clinically. siRNA-induced plasminogen deficiency promoted hepatocyte proliferation after partial hepatectomy in mic...
Product-Intrinsic NF-κB-Driven Transcriptional Programs Connote Durability of CAR-T Response in Multiple Myeloma
Idecabtagene vicleucel (ide-cel) induces deep responses in relapsed/refractory multiple myeloma (RRMM), yet more than half of patients relapse within one year. The intrinsic features of CAR-T products...
A novel triple-knockout allogeneic BCMA CAR T cell therapy (CT0590) in multiple myeloma: preclinical and phase I study
Host-versus-graft reaction (HvGR) is a major challenge in allogeneic chimeric antigen receptor (CAR) T cell therapy. To counter host natural killer (NK) cell attacks, we armored allogeneic, human leuk...