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 Articles

• MYB activity drives emergent enhancer activation and enhancer-promoter interactions in acute lymphoblastic leukemia
• Remodeling 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 Kastritis
• Ikaros 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, MD
• Histidine-rich glycoprotein modulates platelet adhesion and aggregation by binding to GPIbα and GPIIb/IIIa | Jeffery Weitz, MD

In this week's episode, Blood editor Dr. James Griffin interviews Drs. George Goshua, Gerd Blobel, and Paul Kaminski on their latest articles published in Blood. Dr. Goshua elaborates on the background and then insights from "Haploidentical transplant, gene therapy, and standard care in sickle cell disease: a cost-effectiveness analysis". This analysis provides valuable guidance for clinicians, patients, and health systems as they consider treatment choices. However, as concluded in the accompanying Blood Commentary, the true measure of success is not which therapy “wins” the economic argument, but whether each patient receives the therapy best suited to their clinical needs and values. Then, Drs. Gerd Blobel and Paul Kaminski share "Dissecting polycomb complexes for enhanced fetal hemoglobin production", which utilizes a comprehensive CRISPR-based screen to interrogate the components of these repressive complexes and identified a single protein domain in EZH2, a subunit of PRC2, as a potential therapeutic target. They demonstrate that inhibition of the domain encoded by exon 14 of EZH2 selectively derepresses fetal hemoglobin expression, raising the possibility of developing drugs that specifically target this domain to treat hemoglobinopathies.

In this week's episode, Blood editor Dr. Laura Michaelis interviews Drs. Matthew Frank and Jieqing Zhu on their latest articles published in volume 147 issue 22 of Blood. Dr. Frank discusses "How I treat HLH-like toxicities after immune effector cell therapy", in which the two cases presented emphasize the need for early identification, the use of anticytokine therapy with either emapalumab or ruxolitinib when organ toxicities worsen despite conventional CRS-directed treatment, and the need for ancillary supportive care as central to success. Dr. Zhu shares insights from "Structural Basis of HPA-1 a Alloimmunization in FNAIT and Allosteric Regulation of Integrin Conformation" where they probed the structure-function relationships underpinning interactions of alloantibodies against the most common target, human platelet antigen 1a (HPA-1a). Their data can help explain why some alloantibodies cause severe hemorrhagic FNAIT while others result in milder, asymptomatic thrombocytopenia.

In this week's episode, Blood editor Dr. Laura Michaelis interviews Drs. Pierre-Yves Dumas and Samik Basu on their latest articles published in Blood. Dr. Dumas talks about "Prognostic impact of FLT3-ITD microclones in young adults with acute myeloid leukemia treated with intensive chemotherapy" where the team was able to identify that ultra-low-burden FLT3-ITD microclones are associated with higher relapse risk and inferior relapse-free survival. Their work encourages the evaluation of FLT3 inhibitor strategies. Dr. Basu discusses "CD19 CAR T-cell therapy is feasible for patients with pemphigus vulgaris treated without lymphodepletion in the RESET-PV trial". In four patients, the treatment was well tolerated and supported CAR T-cell expansion and persistence, challenging the need for lymphodepletion and supporting chemotherapy-free approaches in autoimmune disease.

In this week's episode, Blood editor Dr. James Griffin interviews Drs. Hanny Al-Samkari and Xin Zhou on their latest articles published in Blood. This episode highlights two important advances in hematology: the first report from the CHORUS registry for hereditary hemorrhagic telangiectasia (HHT) presented by Dr. Al-Samkari and also the introduction of the ASH Hematomics (ASHOP) platform for integrative genomic data analysis presented by Dr. Zhou. The CHORUS registry reveals that HHT is a progressive, underrecognized inherited bleeding disorder with a substantial burden of recurrent bleeding, iron deficiency, arteriovenous malformations, and life-threatening complications, while emphasizing the need for earlier diagnosis and the development of targeted therapies. The second presentation introduces ASHOP, an open-access platform that enables researchers to explore and integrate large-scale clinical and genomic datasets, facilitating discoveries in leukemia and other hematologic diseases through advanced analytical tools. Together, these studies demonstrate how comprehensive patient registries and innovative data-sharing resources are advancing precision medicine, improving disease understanding, and accelerating future research across hematology.