In this week's episode, Blood editor Dr. Laurie Sehn interviews Drs. Shengwen Calvin Li and Hrishi Krishna Srinagesh on their latest articles published in Blood. Dr. Li discusses "Single-cell profiling of ANKRD26 thrombocytopenia reveals progenitor expansion and polyploid apoptosis via JUNB-p21". The study identifies reproducible abnormalities in progenitor expansion and increased apoptosis of polyploid megakaryocytes, and they propose a novel mechanism in which centrosomal over-expression of ANKRD26 drives polyploid megakaryocyte apoptosis through JUNB-mediated induction of p21 transcription. Dr. Srinagesh discusses "Blinatumomab nonresponse correlates with poor survival after brexucabtagene autoleucel in B-cell ALL" in which data collected by the Real-World Outcomes Collaborative of CAR-T in Adult ALL consortium showed that prior nonresponse to blinatumomab was associated with inferior survival after brexucabtagene in comparison to blinatumomab-naïve patients. Early CAR-T responses were uniformly high regardless of prior exposure or response. This highlights that resistance to blinatumomab may identify patients at higher risk of post–CAR T relapse despite excellent initial responses.

In this week's episode, Blood podcast editor Laurie Sehn interviews Drs. Edward Cliff on his latest research published in volume 147 issue 14 of Blood. Dr. Cliff discusses "Global access to commercial CAR T-cell therapies: a cross-sectional study of health technology assessment across the G20 countries" which maps the mismatch between innovation and implementation across high-income and selected-upper-middle-income countries for US Food and Drug Administration–approved products and indications.

In this week's episode, Blood podcast editor Dr. James Griffin interviews authors Drs. Steffen Boettcher and Robert Zeiser on their recent publications in Blood. Dr. Boettcher discusses "Bone marrow failure, somatic rescue by p53 inactivation, and enhanced leukemogenesis in germ line ERCC6L2 disease", which provides insights to disease evolution by demonstrating that p53 loss can rescue BMF phenotypes caused by biallelic mutations in ERCC6L2, but at the cost of profound genome instability, increasing DNA damage and leading to the onset of aggressive erythroid leukemia. Dr. Zeiser discusses "Gastrin for the treatment of acute graft-versus-host-disease of the stomach", which delineates the protective role of gastrin in aGVHD of the stomach in mice and patients and provides a rationale for therapeutic use of pentagastrin in a clinical trial for patients with aGVHD.

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. Carole Peyssonnaux and Ajai Chari on their papers published in volume 146 issue 24 of Blood. The work of Dr. Peyssonnaux 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.