Blood Podcast

In this week's podcast, a potential new therapeutic target in beta-thalassemia. The E3 ubiquitin ligase AMBRA1 promotes autophagic clearance of free alpha-globin. Researchers describe mutations in the AMBRA1 gene that impair this clearance, exacerbating ineffective erythropoiesis and disease severity. After that: targeting MYD88 mutations. Lasalocid-A is a compound that selectively binds to the MYD88 L265P mutant protein, which is found in a range of B-cell lymphomas. New research shows its potential to inhibit tumor growth, overcome ibrutinib resistance, and synergize with venetoclax. Finally: air pollution is linked to an increased risk of venous thromboembolism in a prospective, community-based cohort study. The findings highlight the harms of pollution, and support the case for global efforts to improve public health.Featured Articles:Mutations in AMBRA1 aggravate β-thalassemia by impairing autophagy-mediated clearance of free α-globinLasalocid A selectively induces the degradation of MYD88 in lymphomas harboring the MYD88 L265P mutationAir pollution is associated with increased risk of venous thromboembolism: the Multi-Ethnic Study of Atherosclerosis

In this week's episode we’ll learn more about the significance of hypercalcemia in monoclonal gammopathy of undetermined significance, the role of neutrophil gelatinase-associated lipocalin in hemostasis, and the feasibility of combining CD19-targeted NK- or T-cell therapy with anti-CD19 monoclonal antibodies.Featured Articles:Approaching Hypercalcemia in Gammopathy of Undetermined Significance: Insights from the iStopMM study Deficiency of neutrophil gelatinase-associated lipocalin elicits Hemophilia-like bleeding and clotting disorder Anti-CD19 antibody cotreatment enhances serial killing activity of anti-CD19 CAR-T/-NK cells and reduces trogocytosis 

In this Review Series episode Reflections on a Quarter Century of TKIs in CML introduced by Associate Editor Dr. Jason Gottlieb, we’ll hear from contributing authors Drs. Brian Drucker, Francois Guillot, Tim Hughes and Michael Deininger, as they discuss how CML treatment has been impacted since the introduction of tyrosine kinase inhibitors 25 years ago.Click here to view the complete Review Series featured in Volume 145 Issue 9 of Blood.

In this week's episode, we'll hear about a “belt and suspenders” approach to paroxysmal nocturnal hemoglobinuria, or PNH. We’ll review long-term efficacy data for danicopan—an oral complement factor D inhibitor recently approved as an add-on to C5 inhibitor therapy.After that: researchers show how oral pathogens may exacerbate chronic graft-versus-host disease. And they assess targeted interventions to mitigate these effects. Finally, we move from the oral to the gut microbiome. New findings suggest that intestinal dysbiosis, induced by antibiotics, may adversely affect outcomes among patients who are receiving CAR-T cell therapy.Featured Articles:Long-term efficacy and safety of danicopan as add-on therapy to ravulizumab or eculizumab in PNH with significant EVHOral inflammation and microbiome dysbiosis exacerbate chronic graft-versus-host diseaseAntibiotic-induced loss of gut microbiome metabolic output correlates with clinical responses to CAR T-cell therapy

In this week's episode we’ll find out about longer term results from a pivotal trial of mosunetuzumab in relapsed/refractory follicular lymphoma, potential use of CD70 CAR T-cells that secrete an anti-CD33/anti-CD3 bispecific antibody as a therapy for acute myeloid leukemia, and how ferroptosis regulates hemolysis in stored red blood cells.Featured Articles:Long-term 3-year follow-up of mosunetuzumab in relapsed or refractory follicular lymphoma after ≥2 prior therapiesCD70 CAR T cells secreting an anti-CD33/anti-CD3 dual-targeting antibody overcome antigen heterogeneity in AMLFerroptosis regulates hemolysis in stored murine and human red blood cells

In this Review Series episode on Basic/Translational Science of Factor VIII, Factor IX, and von Willebrand Factor introduced by Dr. Thomas Ortel, we’ll hear from contributing authors Drs. Ben Samuelson Jones, Mac Monroe and Peter Lenting as they discuss how the functional roles of these 3 proteins are interconnected. Click here to view the complete Review Series featured in Volume 144 Issue 21 of Blood.

Discover the promising outcomes from a Phase I study on a new leukemia treatment using dual tyrosine kinase inhibitors. Uncover the role of ferroportin in iron-sensing within liver endothelial cells and its implications for iron homeostasis. Additionally, learn about concerning anemia trends in pregnant patients with beta-thalassemia minor, highlighting the risks of misdiagnosis and unnecessary treatments. This insightful discussion sheds light on critical advancements in hematology and the challenges faced in maternal health.

In this week's episode we’ll learn more about a phase 2 trial of first-line zanubrutinib, obinutuzumab, and venetoclax in TP53-mutated mantle cell lymphoma; early development of hyperdiploidy in multiple myeloma; and a phase 1 trial of the asparaginase pegcrisantaspase plus venetoclax in relapsed/refractory acute myeloid leukemia.Featured Articles:Zanubrutinib, obinutuzumab, and venetoclax for first-line treatment of mantle cell lymphoma with a TP53 mutationDevelopment of hyperdiploidy starts at an early age and takes a decade to completeA phase 1 study of the amino acid modulator pegcrisantaspase and venetoclax for relapsed or refractory acute myeloid leukemia

In this week's episode we'll learn about C3-targeted therapy in autoimmune hemolytic anemias. Based on results of an open-label, phase 2 study, pegcetacoplan was well-tolerated, with encouraging efficacy, particularly in patients with cold agglutinin disease. After that: Venetoclax sensitivity testing to predict AML response. In a significant step toward precision medicine, researchers have validated an assay capable of predicting response to the venetoclax-azacitidine regimen. Finally, an improved basic understanding of human coagulation factor XIII. Investigators present the cryo-electron microscopy structure of Factor XIII complex, providing new insights into etiology and the deleterious effects of certain specific mutations.Featured Articles:Safety and efficacy of pegcetacoplan treatment for cold agglutinin disease and warm antibody autoimmune hemolytic anemiaEx vivo venetoclax sensitivity predicts clinical response in acute myeloid leukemia in the prospective VenEx trialCryo-EM structure of the human native plasma coagulation factor XIII complex

In this Review Series episode on Globin Disorders introduced by Drs. Thomas Coates and Irene Roberts, we’ll hear from Dr. Douglas Higgs and Dr. Mitchell Weiss as they address advances in our understanding of globin gene biology.Click here to view the complete Review Series featured in Volume 144 Issue 8 of Blood.