Blood Podcast

In this episode, Blood Associate Editor Dr. Jason Gotlib discusses the Review Series "The New Wave of Targeted Therapeutics for MPN’s", with authors Drs. Stefan Constantinescu, Ann Mullally, and Marina Kremyanskaya. This Review Series covers 3 areas where exciting advances are occurring. Dr. Constantinescu discusses “Next-generation JAK inhibitors in the treatment of myeloproliferative neoplasms” which describes how new ways to switch off JAK signaling are delivering a suite of new small-molecule drugs with potential. Dr. Mullally discusses “Novel strategies targeting mutant calreticulin in essential thrombocythemia and myelofibrosis” which reviews the biology of calreticulin mutations in myelofibrosis and ET and how multiple different modalities can be brought to bear against this mutant surface protein, including monoclonal antibodies, bispecific T-cell engagers, and cellular and vaccine therapies. Dr. Kremyanskaya discusses “Modulators of the hepcidin pathway in polycythemia vera and myelofibrosis” which outlines the major recent progress being made in controlling excessive erythropoiesis through pharmacological modulation of iron metabolism.

In this week's episode, Blood editor Dr. Laura Michaelis interviews Drs. Alexander Bick and Jorge Cortes on their latest papers published in Blood. Dr. Cortes, the current EIC of Blood Global Hematology discusses "Asciminib Demonstrates Superior Efficacy and Safety in Newly Diagnosed Chronic Myeloid Leukemia in the ASC4FIRST Trial" wherein the planned secondary analysis showed a further efficacy advantage and a consistently favorable safety profile for asciminib relative to investigator-selected TKIs, especially second-generation TKIs. Dr. Bick discusses "Increased prevalence of clonal hematopoiesis in children with sickle cell disease" where targeted sequencing for CH mutations in 2318 children with SCD and 2957 controls and found that children with SCD have a higher prevalence of CH, and majority of CH cases identified were very small “micro-CH” clones, more work is needed to define the clinical significance of these clones.

In this week's episode of the Blood podcast, editor Dr. James Griffin interviews Drs. Christian Gorzelanny and Rebecca Leaf on their latest articles published in this week's issue of Blood. Dr. Gorzelanny discusses compelling evidence for a new mechanism that amplifies their proinflammatory actions in "Lipid nanotubes unmask neutrophils for complement attack", demonstrating the pathological role of this process in a range of inflammatory disorders in order to stimulate intense study of how to regulate nanotube formation for therapeutic benefit. In "Immune thrombocytopenia in patients treated with immune checkpoint inhibitors" Dr. Leaf and colleagues define the incidence, clinical features, and outcomes of ICI-induced immune thrombocytopenia. Showing that ICI-induced immune thrombocytopenia is associated with excess mortality, these data should provide an impetus to greater recognition and to protocolization of effective interventions.

In this week's episode, Blood editor Dr. Laura Michaelis interviews authors Drs. Marion Falabrègue and Ajai Chari on their papers published in volume 146 issue 24 of Blood. The work of Dr. Falabrègue and colleagues in "Intestinal hepcidin overexpression promotes iron deficiency anemia and counteracts iron overload via DMT1 downregulation" indicates that iron absorption from the apical surface of enterocytes can be modulated through manipulation of the hepcidin-DMT1 interaction, opening new avenues for research and therapeutic manipulation. "Talquetamab plus daratumumab in multiple myeloma" features a phase 1b/2 trial of 65 heavily pretreated patients with MM, where Chari et al combined daratumumab and talquetamab, a GPRC5D-targeting bispecific antibody, reporting depletion of CD38-expressing regulatory T cells following daratumumab and impressive efficacy, with an 80% overall (57% complete) response rate and median progression-free survival of 23.3 months. This regimen is now being evaluated in a phase 3 trial.

In this week's episode, Blood associate editor Dr. Laura Michaelis interviews Drs. Mark Sorial and Emmanuelle Passegue on their articles published in volume 147 issue 7 of Blood. Dr. Sorial discusses "Early time to relapse as a survival prognosticator in nodal mature T-cell lymphomas: results from the PETAL consortium" where he and his team evaluated the prognostic significance of early relapse in a large retrospective cohort. They report a time to relapse of <12 months as a strong predictive factor independent of the prognostic index for T-cell lymphoma and histology, with results validated in 2 independent cohorts. Dr. Emmanuelle Passegue discusses "Inflammation perturbs hematopoiesis by remodeling specific compartments of the bone marrow niche". Using a combination of single-cell RNA sequencing profiling and flow cytometry, the team characterized the bone marrow niche compartments in mice subjected to inflammation. They show that inter-feron-mediated inflammation preferentially targets central marrow leptin receptor–expressing mesenchymal cells, triggering cytokine release that affects monocyte dynamics in the bone marrow microenvironment.

This review series focuses on recent advances in resolving macro and molecular structures that have driven the field of occlusive thrombus structure and function forward. Covering multiple contributions to thrombosis, eg, platelets, factor XIII, and the contact system, the series also looks to put this new knowledge into the context of future advances in diagnostic and therapeutic tools to enhance normal hemostasis while preventing and treating unwanted thrombosis. Blood Associate Editor, Dr. Thomas Ortel discusses this series with Drs. Alisa Wolberg, Jonas Emsley, and John Weisel, who all contributed to articles in the Review Series on the Structural Underpinnings of Hemostatic Plugs and Thrombotic Occulsions which can be found in volume 146, issue 12 of Blood.

In this week's episode, Blood editor Dr. Laurie Sehn interviews authors Drs. Julie Jaffray and Ulrike Philippar on their latest articles published in Blood. Dr. Jaffray discusses her CME article, "Multisite validation of a venous thrombosis risk model in critically ill children through the CHAT Consortium", identifying patients with risks as high as 17% and taking research one step closer to the goal of personalized thromboprophylaxis for safe and effective care of high-risk children. Dr. Philippar discusses her article "Ramantamig (JNJ-79635322), a novel T-cell-engaging trispecific antibody targeting BCMA, GPRC5D, and CD3, in multiple myeloma models", where the extensive in vitro and in vivo preclinical studies with cell lines and patient samples indicate strong potential for this agent to have efficacy against MM expressing either or both of these antigens.

In this week's episode, Blood editor Dr. Laurie Sehn interviews authors Drs. Anastasios Karadimitris and Maria Carolina Florian on their papers published in Volume 147 Issue 2 of Blood. Dr. Karadimitris' paper "Off-the-shelf dual CAR-iNKT cell immunotherapy eradicates medullary and leptomeningeal high-risk KMT2A-rearranged leukemia", discusses the success of bispecific CAR-iNKT cells targeting CD19 and CD133 in pre-clinical models, prompting the clinical development of this class of product. Dr. Florian's paper, "A Notch trans-activation to cis-inhibition switch underlies hematopoietic stem cell aging" proposes that the Jagged2/Notch interaction is a key regulator of hematopoietic stem cell divisional symmetry during aging and offers insights that may inform strategies to restore regenerative function in aged hematopoiesis.