Restoring Stem Cell Function After Iron Overload

In this week's episode, Blood editor Dr. Natalie Rosen interviews Dr. Lindsey George, Director of Clinical In Vivo Gene Therapy and an attending physician in the Division of Hematology at Children's Hospital of Philadelphia, and also Dr. Miles Horton and Dr. Thomas Lew of the Royal Melbourne Hospital and Peter McCallum Cancer Center, and the Walter and Eliza Hall Institute of Medical Research on their latest articles published in Blood on the characterization of the prothrombotic mechanisms of recombinant FVIII Aurora and turning immunosuppressants into tools for bidirectional in vivo control. Dr. George discusses "Factor VIII Aurora: a naturally occurring gain-of-function FVIII variant with enhanced FIXa affinity" and Drs. Horton and Lew discuss "Prime editing enables drug-controllable T-cell therapies with clinical immunosuppression".

In this week's episode, Blood editor Dr. Laurie Sehn interviews Dr. Andrew Lane from the Dana-Farber Cancer Institute and Dr. Pooja Khandelwal from the Cincinnati Children's Hospital Medical Center on their latest articles published in Blood on new drug combinations for BPDCN and reduced intestinal dysbiosis after HSCT. Dr. Lane discusses "Tagraxofusp, azacitidine, and venetoclax for blastic plasmacytoid dendritic cell neoplasm" and after, Dr. Khandelwal discusses "Human milk oligosaccharide (2′-FL) modifies the gut microbiome in children after bone marrow transplant".

In this week's episode, Blood editor Dr. Laurie Sehn interviews Dr. Annamaria Aprile of the San Raffaele Telethon Institute for Gene Therapy on her latest article published in Blood titled "Iron overload damages mitochondria and induces metabolic rewiring of hematopoietic stem cells toward glycolysis." Dr. Aprile describes how reducing iron and mitochondrial reactive oxygen species in vivo restores mitochondrial activity, quiescence, and the self-renewal of HSCs. She discusses the therapeutic implications of these findings, focusing on combining iron chelation with a mitochondrial-focused antioxidant to protect or restore stem cell function, a strategy that still needs further testing, including in patient-derived cells.

In this week's episode, Blood editor Dr. Laura Michaelis interviews Dr. Moritz Fürstenau of University Hospital Cologne and Dr. William Dunn of the University of Cambridge on their latest articles published in Blood on CLL and clonal monocytosis. Dr. Fürstenau discusses "Venetoclax combinations in untreated CLL: 5-year results and patient-reported outcomes analysis of the CLL13/GAIA trial" highlighting greater improvements in patient-reported quality of life.  Dr. Dunn discusses "The prevalence and clinical significance of clonal monocytosis" describing how using sex-specific monocyte thresholds and excluding isolated DNMT3A mutations refines the association between CMUS and MN.

In this week's episode, Blood editor Dr. Laurie Sehn interviews Drs. Dan Chalothorn and David Gutstein from Regeneron Pharmaceuticals, and Dr. Ajitha Thanabalasuriar from McGill University on their latest articles published in Blood. The first half of the episode features "Anticoagulation with the mechanistically distinct FXI/FXIa antibodies amrecibart (REGN9933 A2 ) and cenvacibart (REGN7508 Cat )" during which Drs. Chalothorn and Gutstein discuss their research on anticoagulants targeting Factor XI and Factor XIa, which showed promising preclinical results in reducing thrombosis without increasing bleeding risk. They developed two distinct antibodies, targeting different domains of Factor 11, offering potential treatment options for different patient profiles. Next, while discussing "TGF-β–PDL1 signaling in neutrophils preserves the lung barrier during hyperinflammation", Dr. Thanabalasuriar underscores that dissecting neutrophil-specific TGF‑β/PD‑L1 signaling in real ICU patients is essential to translate this pathway into truly personalized therapies that both preserve lung barrier integrity and prevent fatal hyperinflammatory injury.

In this week's episode, Blood editor Dr. Laura Michaelis interviews Dr. Harry Erba of Duke University and Dr. Sairah Ahmed of the University of Texas MD Anderson Cancer Center on their latest articles published in Blood on durable treatment strategies for relapsed and refractory hematologic malignancies. Dr. Erba discusses "Ziftomenib with venetoclax and azacitidine for relapsed/refractory NPM1-mutated acute myeloid leukemia" highlighting the promise of this triplet regimen in a high-risk relapsed setting and delving into the mechanistic differences among menin inhibitors.  Dr. Ahmed discusses "Durable efficacy and manageable long-term safety of lisocabtagene maraleucel for 3L+ FL: 3-year update from TRANSCEND FL" reviewing the 94% complete response rate, long-term safety profile, and how clinicians can decide whether a patient with relapsed follicular lymphoma is better suited for a bispecific antibody or CAR T-cell therapy.

In this week's episode, Blood editor Dr. James Griffin interviews Dr. Jianxiang Wang from the National Clinical Research Center for Blood Diseases and the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College in Tianjin, China, on his latest article published in Blood titled "Venetoclax plus pediatric regimen in adolescents and adults with Ph-negative acute lymphoblastic leukemia." In this prospective phase 2 study, 167 adolescents and adults (aged 14-60 years) with ND Ph− ALL received a course of venetoclax combined with pediatric-inspired chemotherapy, to determine the results of this treatment on MRD negativity.

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.