Blood Podcast

In this week's episode, Blood editor Dr. Laurie Sehn interviews Drs. Mariateresa Fulciniti and Angelo D'Alessandro on their latest articles published in Blood. Dr. Fulciniti, of the Dana Farber Cancer Institute, discusses the development of "PKMYT1 is a targetable vulnerability in del(17p) high-risk multiple myeloma" starting from the question, "Is 17P loss simply a prognostic marker, or does it create specific vulnerabilities that we can therapeutically exploit?" Then, Dr. D'Alessandro, of the University of Colorado, discusses "The red blood cell proteome and interactome identify a Band 3–BLVRB axis regulating hypoxic metabolic adaptation." His team began by asking, "What's in a red blood cell? How many proteins are there, and how can we confidently claim that these now several 1000s of proteins in opposite excess are indeed proteins within red blood cells are not coming from contaminants?" Both studies describe how deep molecular profiling can uncover specific, potentially targetable biological dependencies or interaction axes that may enable more precise, mechanism‑based therapeutic strategies.

In this week's episode, Blood editor Dr. James Griffin interviews Drs. Thomas Milne and Dominique Bonnet on their latest articles published in volume 147 issue 24 of Blood. Dr. Milne discusses how transcription factors simultaneously activate enhancers and connect them to their target genes in KMT2A-rearranged acute lymphoblastic leukemia. The binding of MYB, a key hematopoietic TF, is sufficient to drive novel enhancer activation, including initiating 3D contact with target promoters to drive ectopic expression of distal oncogenes.  Continued MYB binding is required to maintain enhancer-promoter interactions, indicating that disruption of MYB is therapeutically tractable in multiple leukemias. Then, considering bone marrow vasculature, Dr. Bonnet discusses how the use of in vivo models to identify selective injury to sinusoidal endothelial cells caused by venetoclax-azacitidine, revealed a therapy-associated mechanism that links BM niche damage to impaired hematopoietic recovery. These data help explain the prolonged BM hypoplasia observed in some patients and prompt further research into how other targeted therapy-based induction regimens influence the BM microenvironment.Featured ArticlesMYB activity drives emergent enhancer activation and enhancer-promoter interactions in acute lymphoblastic leukemiaRemodeling of the bone marrow vasculature induced by venetoclax and azacitidine damage

In this week's episode, Blood editor Dr. Laurie Sehn interviews Drs. Camille Laurent and Christine Bezombes on their latest article published in Blood titled "Patient-derived lymphoma spheroids reveal predictive markers of glofitamab resistance in relapsed/refractory B-NHL." By using patient-derived lymphoma spheroids as an ex vivo platform, they identify key mechanisms of resistance to the bispecific T-cell engager glofitamab in B-cell non-Hodgkin lymphoma, showing that higher CD8 T-cell abundance and cytotoxic activity is associated with better therapeutic responses, while increased T follicular helper (Tfh) cells correlate with resistance. The authors further show that resistance could be overcome by depleting Tfh cells or combining glofitamab with TIGIT (T-cell immunoreceptor with Ig and ITIM domains) blockade, highlighting promising strategies to improve responses to T-cell engager therapies.

In this week's episode, Blood editor Laurie Sehn interviews Drs. Efstathios Kastritis and Lucia Chen on their latest articles published in Blood. Dr. Kastritis shares insights and results from the final survival analysis of the ANDROMEDA trial, which determined that adding daratumumab to cyclophosphamide, bortezomib, and dexamethasone improves hematologic responses and overall survival in newly diagnosed AL amyloidosis.  Dr. Chen elaborates on the key benefits of Ikaros degradation for reducing T-cell dysfunction in MM patients: Ikaros degradation by mezigdomide enhances anti–B-cell maturation antigen CAR-T and bispecific TCE therapy efficacy in vitro and in vivo. Featured Articles: Daratumumab-Bortezomib-Cyclophosphamide-Dexamethasone for Newly Diagnosed Amyloidosis: ANDROMEDA Final Survival Analysis | Efstathios KastritisIkaros degradation by mezigdomide reduces T-cell dysfunction and improves the efficacy of antimyeloma T-cell therapies | Lucia Chen

In this week's episode, Blood editor Dr. Laura Michaelis interviews Drs. Joshua Hill and Jeffery Weitz on their latest articles published in Blood. Dr. Hill and Dr. Michaelis discuss the evolving landscape of infection risk in adults receiving bispecific antibody therapies for advanced B‑cell malignancies. They explore how these risks differ from those seen with allogeneic transplant, CAR T‑cell therapy, and traditional CD20‑directed antibodies, and touch on emerging approaches such as trispecific antibodies and evolving strategies for supportive care, including immunoglobulin replacement. In the second half of the episode, Dr. Michaelis is joined by Dr. Jeffrey Weitz to discuss new insights into the role of histidine‑rich glycoprotein in hemostasis. Their conversation delves into HRG’s interactions with key platelet receptors, its behavior in inflammatory states like sepsis and COVID‑19, and how these observations may reshape thinking about thrombosis risk and future therapeutic approaches.Featured Articles: How I prevent infections in adults receiving bispecific antibody therapies for advanced B-cell malignancies | Joshua Hill, MDHistidine-rich glycoprotein modulates platelet adhesion and aggregation by binding to GPIbα and GPIIb/IIIa | Jeffery Weitz, MD