Defining Lineage in Ambiguous Leukemia: A Transcriptomic View - Dr. Anikó Sijs-Szabó & Roger Mulet Lázaro, PhD

Could making CAR T cells directly inside the patient change how treatment is delivered? Scientific Editor Dr Charles De Bock joins Prof Roch Houot, Dr Jaime Fuentealba, François Vilcot, PharmD, and Carole-Anne Brugère, PharmD, to explore the promise and challenges of in vivo CAR therapy. They compare delivery approaches, examine safety and targeting, and discuss potential gains in access alongside uncertainty over costs. Listen for a multidisciplinary perspective on what comes next.Read the referenced Review Article here: https://bit.ly/4d1mfjPKey topicsHow in vivo CAR therapy differs from conventional CAR T manufacturingLentiviral vectors and lipid nanoparticles: targeting, persistence, and safety, including the need for long-term monitoringClinical translation, scalability, and why simpler delivery may not mean lower pricesEurope’s role in development and lessons from writing a multidisciplinary reviewTimestamps00:00 — Why in vivo CAR is attracting attention now 02:37 — What it means to manufacture CAR T cells inside the patient 05:29 — Three layers of specificity for lentiviral delivery 10:08 — Why modern lentiviral vectors are safer than early gene therapy vectors 14:41 — How lipid nanoparticles can target T cells and avoid the liver 16:26 — Whether transient CAR expression can still be therapeutic 19:10 — Choosing between lentiviral vectors and lipid nanoparticles 22:53 — The hardest unsolved problem: balancing efficacy, safety, and scalability 23:18 — Site-specific gene editing and TRAC locus insertion 26:21 — Industry momentum and whether in vivo CAR can lower cost 28:40 — Europe’s opportunity in clinical translation 31:23 — What to expect from upcoming ASH and other conference data 35:05 — How the multidisciplinary review was scoped and organized 37:09 — Why figures were designed early in the writing process 39:57 — Advice for PhD students writing a review in a fast-moving field

This episode explores how chronic myeloid leukemia has been transformed by imatinib and other TKIs, while also showing why major clinical challenges remain for the patients who do not respond well or want to stop therapy. Host Scientific Editor Dr Charles de Bock talks with Dr. Ilaria Pagani about her recent HemaSphere paper on mitochondrial DNA mutations, oxidative phosphorylation, and treatment response in CML, and why mitochondria may be an overlooked source of biomarkers and new targets. We discuss the biology of relapse, why some patients can achieve treatment-free remission, and how mitochondrial metabolism may help explain differences between poor responders and super responders. The conversation also touches on patient advocacy, quality of life, and the need for more collaborative, metabolism-focused research.Read the article in full, open access: https://hsphere.pub/448You've read the paper, now hear the story.

In this episode, host Dr Charles de Bock delves into groundbreaking preclinical research exploring the potential of tasquinimod to restore blood cell production and modify the bone marrow microenvironment in MDS with Dr Manja Wobus and Dr Katja Sockel. Join us as we unpack the mechanisms, animal studies, and future clinical prospects for this promising therapy.Read the accompanying article published in HemaSphere https://bit.ly/3OjuuiSi4MDS, EHA's Specialized Working Group information https://hsphere.pub/5d4

Discover the latest insights into the multifaceted role of p53 in normal hematopoiesis and its critical involvement in myeloproliferative neoplasms (MPNs). This episode features Dr. Isabelle Plo and Dr. Barbara Monte-Mór sharing their expertise on TP53 mutations, molecular mechanisms driving leukemic transformation, and emerging therapeutic strategies targeting p53.Article: https://bit.ly/4sZbo01Comments, Suggestions or Feedback? Please take a few minutes and let us know: https://wkf.ms/4pDYjYb

In this episode, host HemaSphere Scientific Editor Dr Charley de Bock speaks with Associate Professor Dr Matthew Greenwood about the SUBLIME (ALL09) trial, which explores replacing consolidation chemotherapy with blinatumomab in adolescents and young adults with B‑cell ALL. They discuss why immunotherapy may outperform traditional cytotoxic approaches, how MRD‑guided treatment is reshaping risk stratification, and what future protocols might look like as genomic and immune‑response data are integrated in real time. Dr. Greenwood also shares upcoming innovations—including menin inhibitors, venetoclax‑based MRD targeting, and adaptive platform designs—along with honest insights into the challenges of running clinical trials across Australia.

In this extended episode of the HemaSphere podcast, based on a must-read Perspective "Can health inequalities in sickle cell disease be addressed through novel therapies?", our host Scientific Editor Charles de Bock discusses sickle cell disease with co-authors, covering both expert and lived-patient perspectives. They explore the complexities of living with the disease, the current treatment landscape, and highlight the ongoing health inequalities faced by patients, the impact of withdrawn therapies, and the need for improved communication and trust between patients and healthcare providers.Further information:No One's Listening ReportShaniqua's Sickle ChroniclesNICE (National Institute for Health and Care Excellence)UK NHS blood donationPlease take a few minutes and let us know what you think about this episode! Podcast Feedback

Dr. Anikó Sijs-Szabó & Roger Mulet Lázaro, PhD, join Dr. Charles de Bock to unpack the challenges of diagnosing and treating acute leukemias of ambiguous lineage (ALAL). Discover how RNA sequencing, machine learning, and collaboration are shaping the future of precision medicine in hematology. 🎧 Listen and then read the full open-access article on the HemaSphere website https://bit.ly/4oeJo6w

Join our host HemaSphere Scientific Editor Dr Charles de Bock as he chats with Dr Kai Rejeski, first author of this 2025 HemaSphere Top Cited –Clinical Award-winning paper. The conversation delves into the complexities of CAR-T therapy, particularly focusing on the associated toxicities and the need for a structured grading system.EHA/EBMT Survey on Grading and Management of ICAHT, is on our website and all major podcast platforms (Spotify, Apple Podcast, and more) and YouTube. Listen and enjoy casual, insightful discussions about #hematology research.You can find the referenced article, in full and open access, here on the HemaSphere website.

Host Dr Charles de Bock speaks with Prof Michel Zwaan and Prof Olaf Heidenreich, co-authors from the 2025 HemaSphere Award - Top Cited: Biology paper, "The MLL-Menin Interaction is a Therapeutic Vulnerability in NUP98-rearranged AML." The conversation delves into the complexities of #AML, particularly focusing on NUP98 rearranged AML and the therapeutic potential of Menin inhibitors. The discussion highlights the challenges in treating this aggressive form of leukemia, the mechanisms of menin inhibitors, and the importance of combining therapies to improve patient outcomes. Season 3, Episode 5: Tackling NUP98 Rearranged AML in Pediatric Oncology, is on our website and all major podcast platforms. Listen and enjoy casual, insightful discussions about #hematology research.

In this second part of a 2-part episode, Dr Charles De Bock engages with Prof Dr Petya Apostolova and Dr Jörg Büscher to explore the intricate relationship between metabolism and hematology, particularly focusing on #AML. They discuss the challenges and advancements in metabolomics, the importance of integrating multi-omics approaches, and the future directions of research in this field. The conversation highlights the need for a deeper understanding of metabolic pathways and their implications for cancer treatment, emphasizing the significance of context in cellular behavior and the potential of spatial metabolomics."Metabolism in hematology, Part 2”, is on our website, all major podcast platforms, and YouTube. Listen and enjoy casual, insightful discussions about #hematology research. You can find the referenced Review article, in full and open access, here on the HemaSphere website.