Blood Podcast

In this week's episode, we'll learn about the role of a platelet-specific glycoprotein receptor in abdominal aortic aneurysm formation, the influence of TP53 mutations on outcomes for patients with 5q-deleted myelodysplastic syndrome, and a rational combination treatment intended to produce more durable responses in patients with refractory B-cell acute lymphoblastic leukemia who are treated with CAR T-cell therapy.Featured Articles:Soluble glycoprotein VI predicts abdominal aortic aneurysm growth rate and is a novel therapeutic targetInfluence of TP53 gene mutations and their allelic status in myelodysplastic syndromes with isolated 5q deletionA phase 1 clinical trial of NKTR-255 with CD19-22 CAR T-cell therapy for refractory B-cell acute lymphoblastic leukemia

In this week's episode we'll learn about refining risk stratification in T-cell acute lymphoblastic leukemia, or ALL. After that, we'll discuss a novel gene therapy approach in severe alpha-thalassemia. Investigators describe an innovative mouse model and an effective gene therapy approach, renewing prospects for the development of novel strategies to treat this disease. Finally, we'll hear about how genomic profiling has helped identify subgroups associated with distinct clinical phenotypes and outcomes in the molecular taxonomy of myelodysplastic syndromes, or MDS. Featured Articles NGS-based stratification refines the risk stratification in T-ALL and identifies a very-high-risk subgroup ofpatientsUse of HSC-targeted LNP to generate a mouse model of lethal α-thalassemia and treatment via lentiviralgene therapyMolecular taxonomy of myelodysplastic syndromes and its clinical implications

In this week's episode we’ll discuss a novel tripartite fusion drives treatment resistance in acute promyelocytic leukemia. In some patients with atypical APL, these novel retinoic acid receptor gene fusions result in truncation of the ligand binding domain of the retinoic acid receptor protein, resulting in non-responsiveness to treatment with all-trans retinoic acid. After that: managing immune thrombotic thrombocytopenia or iTTP without therapeutic plasma exchange, or TPE. Finally, hope for motherhood after allogeneic HCT.Featured Articles: Critical role of tripartite fusion and LBD truncation in certain RARA- and all RARG-related atypical APLManagement of immune thrombotic thrombocytopenic purpura without therapeutic plasma exchangeHope for motherhood: pregnancy after allogeneic hematopoietic cell transplantation (a national multicenter study)

In this week's episode we’ll discuss the safety and efficacy of pirtobrutinib with or without rituximab in relapsed/refractory CLL; learn more about erythroid 5ALA synthesis disorders and their conditional synthetic lethal dependency on pyridoxine; and discuss how targeting PKC alpha alleviates iron overload in diabetes and hemochromatosis through the inhibition of ferroportin.Featured Articles:Fixed-duration pirtobrutinib plus venetoclax with or without rituximab in relapsed/refractory CLL: Phase 1b BRUIN trialMurine models of erythroid 5ALA synthesis disorders and their conditional synthetic lethal dependency on pyridoxineTargeting PKCα alleviates iron overload in diabetes and hemochromatosis through the inhibition of ferroportin

In this week's episode we'll discuss outcomes following hematopoietic stem cell transplantation in pediatric patients with Fanconi anemia. Then, we'll learn about how new research shows that the transcription factor Foxo1, commonly associated with glucose metabolism, regulates hepcidin expression and systemic iron homeostasis. Finally, in Latin America: using clinical networks to improve outcomes in patients with acute promyelocytic leukemia. After clinical networks were established, survival and relapse rates improved substantially, highlighting the effectiveness of this unique intervention strategy in low- and middle-income countries.Featured Articles: Outcomes of hematopoietic stem cell transplantation in 813 pediatric patients with Fanconi anemiaFoxo1 is an iron-responsive transcriptional factor regulating systemic iron homeostasisClinical networking results in continuous improvement of the outcome of patients with acute promyelocyticleukemia

In this week's episode we’ll discuss how CD8+ T-cell differentiation and dysfunction inform treatment response in acute myeloid leukemia; learn more about the effect of ATM germline pathogenic variants on the outcomes in children with ataxia-telangiectasia and hematological malignancies; and discuss the preclinical efficacy of a potent, selective menin-KMT2A inhibitor JNJ-75276617 in KMT2A- and NPM1-altered leukemias.Featured Articles:CD8+ T-cell differentiation and dysfunction inform treatment response in acute myeloid leukemiaATM germ line pathogenic variants affect outcomes in children with ataxia-telangiectasia and hematologicalmalignanciesPreclinical efficacy of the potent, selective menin-KMT2A inhibitor JNJ-75276617 (bleximenib) inKMT2A- and NPM1-altered leukemias

In this week's episode we'll discuss HA-1-targeted T-cell receptor T-cell therapy for recurrent leukemia after hematopoietic stem cell transplantation. Next, we'll learn about how 4D intravital imaging in mice reveals the key role of platelets as a source of procoagulant membranes in hemostasis. Finally, we'll hear about modifications to a common induction and maintenance treatment for treatment-naïve mantle-cell lymphoma.Featured ArticlesHA-1–targeted T-cell receptor T-cell therapy for recurrent leukemia after hematopoietic stem celltransplantation4D intravital imaging studies identify platelets as the predominant cellular procoagulant surface in a mousehemostasis modelRandomized study of induction with bendamustine-rituximab ± bortezomib and maintenance withrituximab ± lenalidomide for MCL

In this week's episode we’ll discuss the outcomes of younger patients with mantle cell lymphoma experiencing late relapse; learn more about mass spectrometry-based assessment of M-protein in peripheral blood during maintenance therapy in multiple myeloma and discuss in vivo CAR T-cell generation in non-human primates using lentiviral vectors.Featured Articles: Outcomes of younger patients with mantle cell lymphoma experiencing late relapse (>24 months): the LATE-POD studyMass spectrometry–based assessment of M protein in peripheral blood during maintenance therapy inmultiple myelomaIn vivo CAR T-cell generation in nonhuman primates using lentiviral vectors displaying a multidomain fusion ligand

Introduced by Associate Editor Dr. Thomas Ortel, this bonus episode discusses the Review Series on Factor XI, published in volume 143 issue 15 of Blood Journal. Dr. Ortel is joined by contributing authors Owen McCarty, PhD, Gili Kenet, MD, and David Gailani, MD. Review Series Articles: Introduction to a review series on factor XIBiology of factor XITargeting factor XI and factor XIa to prevent thrombosisFactor XI deficiency: phenotypic age-related considerations and clinical approach towards bleeding risk assessment

In this week's episode we'll learn how cytomegalovirus infection early in life depletes preleukemic cells in a mouse model of B-cell acute lymphoblastic leukemia. After that we'll discuss new research, where GVHD targets organoid-forming bile duct stem cells in a TGF-beta-dependent manner. Conversely, a TGF-beta inhibitor protects these stem cells against GVHD and mitigates biliary dysfunction. Finally, we'll hear about the seven-year outcomes for venetoclax-ibrutinib in relapsed or refractory mantle cell lymphoma. In addition to long-term survival benefits, researchers report durable treatment-free remissions and effective retreatment in patients with MRD-negative complete responses. Featured Articles: Early-life infection depletes preleukemic cells in a mouse model of hyperdiploid B-cell acute lymphoblasticleukemiaGVHD targets organoid-forming bile duct stem cells in a TGF-β–dependent mannerSeven-year outcomes of venetoclax-ibrutinib therapy in mantle cell lymphoma: durable responses andtreatment-free remissions