Blood
Articles in this Issue
Daratumumab-Bortezomib-Cyclophosphamide-Dexamethasone in Newly Diagnosed Amyloidosis: ANDROMEDA Final Survival Analysis
In the primary analysis of ANDROMEDA, addition of subcutaneous daratumumab to bortezomib/cyclophosphamide/dexamethasone (D-VCd) significantly improved hematologic complete response (CR) rate versus VC...
How we prevent infections in adults receiving bispecific antibody therapies for advanced B-cell malignancies
T-cell engaging bispecific antibodies (BsAbs) have transformed the treatment landscape for multiple hematologic malignancies and are under investigation in the frontline setting, within combination re...
Mezigdomide reverses T-cell exhaustion through degradation of IKZF1/IKZF3 and reinvigoration of cytokine production pathways
T cell exhaustion has been shown to be a key resistance mechanism to efficacy of T cell engagers (TCE) in multiple myeloma (MM). Mezigdomide, a potent cereblon E3 ligase modulator that targets IKZF1 a...
Ikaros degradation by mezigdomide reduces T-cell dysfunction and improves the efficacy of antimyeloma T-cell therapies
T cell dysfunction is an important contributor to both multiple myeloma (MM) disease progression and failure of anti-myeloma chimeric antigen receptor (CAR) T cell and bispecific T cell engager (TCE)...
Bone Marrow Stem Cell Connexins: Misconceptions and New Insights
Hematopoietic regeneration requires coordinated activation of hematopoietic stem and progenitor cells (HSPCs) and adaptive remodeling of the bone marrow (BM) microenvironment to meet extreme metabolic...
JMJD1C-mediated epigenetic control of autoimmunity and HIT antibody production
Heparin-induced thrombocytopenia (HIT) is a common drug-induced immune disorder occurring in a subset of heparin-treated patients. Immune complexes comprising heparin, platelet factor 4 (PF4), and PF4...
Genetics and MRD for therapy allocation in adults with Philadelphia chromosome-negative acute lymphoblastic leukemia
In adults with Philadelphia chromosome-negative (Ph-) acute lymphoblastic leukemia (ALL) genetic risk is usually combined with measurable residual disease (MRD) assignment to consolidation therapy. Ho...
Inhibiting thromboinflammation via interleukin-4 binding to platelet glycoprotein VI and suppression of thrombosis
Inflammation and coagulation are intricately linked. Although some studies have documented pro-inflammatory drivers of coagulation, the role of anti-inflammatory cytokines and the underlying mechanism...
Expression of cFLIP in B cells is essential for diffuse large B-cell lymphoma pathogenesis
Diffuse large B cell lymphoma (DLBCL) is a highly heterogenous malignant disease that remains a major clinical challenge as relapsed and refractory disease is difficult to treat. Apoptosis evasion is...
Erythroid-produced intact FGF23 is a paracrine inhibitor of erythropoiesis
Fibroblast growth factor 23 (FGF23) is a phosphate-regulating hormone produced by osteocytes. In iron deficiency anemia (IDA) and in chronic kidney disease (CKD), FGF23 is also produced by erythroid c...
IFNγ Drives Long-Term Bone Marrow Niche Dysfunction Following Doxorubicin-Based Chemotherapy
Cancer survivors experience long-term skeletal and hematopoietic complications that limit quality of life following chemotherapy (CTX), yet the mechanisms underlying these defects remain incompletely...
T cells dressed up with a dual HLA-restricted TCR targeting cathepsin G drive effective AML eradication
Despite immunosensitivity, genetic heterogeneity, low mutational burden and lack of tumor-specific antigens hinder immunotherapy success for acute myeloid leukemia (AML). T cell receptors (TCRs) offer...
tRNA-m1A Modification Safeguards Fetal Liver HSPCs from DNA Damage via Maintaining Iron Homeostasis
Hematopoietic stem and progenitor cell (HSPC) development requires finely tuned gene expression programs, yet the role of tRNA modifications in this process remains largely unknown. Here, we uncover t...
Mechanisms of resistance to Tmprss6 antisense oligonucleotides in a mouse model of β-thalassemia
Non-transfusion dependent β-thalassemia (NTDT) is characterized by ineffective erythropoiesis, suppression of hepcidin, and iron overload, which is a major cause of morbidity and mortality. Hepatic pr...
IGH::FENDRR and specific KRAS mutations define a novel B-ALL molecular subtype with poor chemotherapy response
Large scale sequencing efforts have defined up to 27 diagnostic entities in B-ALL, leaving few samples without subtype assignment. Extended genomic and transcriptomic profiling in routine diagnostics...
TCR T cells targeting IgA- and IgG-expressing multiple myeloma
T cell-based therapies have shown remarkable efficacy in multiple myeloma (MM), yet the disease remains largely incurable. Here, we investigated the constant domains of the immunoglobulin heavy chain...
Eliminating The Need for Sequential Confirmation of Response in Multiple Myeloma
Disease response and progression assessment in multiple myeloma (MM) is based on various measurements of monoclonal protein (serum and urine protein electrophoresis, serum free light chain (FLC, and o...
Hitting the Therapeutic Bullseye with Targeted Therapy for Patients with Chronic Lymphocytic Leukemia
Chronic lymphocytic leukemia (CLL) is a disease of great clinical and biologic heterogeneity; some patients are observed for years without symptoms, while others rapidly develop progressive disease re...
CRISPR-Cas13d functional transcriptomics reveals widespread isoform-selective cancer dependencies on lncRNAs
Long noncoding RNAs (lncRNAs) are a significant yet largely uncharted component of the cancer transcriptome, with their isoform-specific functions remaining poorly understood. In this study, we employ...
Sequential combinations of rapid immunoassays for prompt recognition of heparin-induced thrombocytopenia
Early recognition and treatment of heparin-induced thrombocytopenia (HIT) are crucial to prevent severe complications. While immunoassays offer rapid diagnosis, their sensitivity and specificity are s...
Transcriptional remodeling shapes therapeutic vulnerability to necroptosis in acute lymphoblastic leukemia
Insufficient eradication of cancer cells and survival of drug tolerant clones are major relapse driving forces. Underlying molecular mechanisms comprise activated pro-survival and anti-apoptotic signa...
BLAST: A Globally Applicable and Molecularly Versatile Survival Model for Chronic Myelomonocytic Leukemia
We sought to develop a survival model in chronic myelomonocytic leukemia (CMML) that is primarily based on clinical variables and examine additional impact from mutations and karyotype. 457 molecularl...
T-ICAHT: Grading and Prognostic Impact of Thrombocytopenia After CAR T-cell Therapy
Immune effector cell-associated hematotoxicity (ICAHT) was recently introduced as a distinct toxicity category of CAR-T therapy. While a grading system based solely on neutrophil counts was proposed (...
Outcomes of PLAT-02 and PLAT-03: Evaluating CD19 CAR T-Cell Therapy and CD19-expressing T-APC Support in Pediatric B-ALL
This study reports outcomes of PLAT-02, a phase 2 trial of SCRI-CAR19, a second-generation CAR T-cell product with FMC63 scFv and 41BB costimulation, in pediatric and young adult patients with B-cell...