Editorial Note: The 66th Annual Meeting of the American Society of Hematology (ASH) took place from December 7 to 10, 2024, in San Diego, USA. Renowned as the largest international academic event in hematology, the conference showcased cutting-edge research and the latest advancements in drug development, representing the highest academic standards in the field. At this prestigious event, Dr. Huafeng Wang’s team from The First Affiliated Hospital of Zhejiang University School of Medicine presented four impactful studies. These investigations spanned new therapeutic strategies for myelodysplastic syndrome (MDS) and insights into the mechanisms, potential treatments, and prognostic implications for acute myeloid leukemia (AML). To delve deeper into these findings, Oncology Frontier - Hematology Frontier invited Professor Wang to provide expert commentary and analysis.

Study 1: Lisaftoclax (APG-2575) Combined with Azacitidine for Treating Myelodysplastic Syndrome (MDS)

Abstract No.: 3202

Dr. Huafeng Wang::Despite years of research, the treatment of high-risk MDS has seen limited progress. Hypomethylating agents (HMAs) remain the current standard, but their efficacy often falls short. Given the older age, poor bone marrow function, and frequent comorbidities in MDS patients, ensuring treatment safety has become a significant challenge. Our study explored the novel BCL-2 inhibitor Lisaftoclax combined with azacitidine, demonstrating high efficacy, mild bone marrow suppression, and a low incidence of treatment-related infections with minimal severity. Notably, early mortality was zero. This combination offers a promising alternative for treating refractory MDS, with the potential to redefine the standard of care, extend survival, and benefit more patients.

Study 2: Uncovering Bone Marrow Heterogeneity in AML Patients Using Spatial Transcriptomics and Single-Cell Sequencing

Abstract No.: 2215

Dr. Huafeng Wang::While single-cell sequencing (scRNA-seq) and immunofluorescence have shed light on AML’s bone marrow microenvironment heterogeneity and highlighted the role of leukemia stem cells (LSCs), spatial transcriptomic analysis remains a significant challenge in hematologic diseases. Our study introduces SPOT-seq, a novel decalcification-based approach that preserves mRNA integrity while mapping the spatial transcriptomics of AML bone marrow. Integrating spatial transcriptomics, single-cell sequencing, and histopathology, we observed that a higher proportion of stem-like tumor cell subpopulations reside near the endosteal niche, with specific gene expression correlating with proximity to this niche. SPOT-seq provides a robust method for analyzing spatial transcriptomics in human bone marrow, paving the way for deeper insights into AML biology.

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Study 3: Mitochondrial Deficiencies and Metabolic Features in Early T-Cell Precursor Acute Lymphoblastic Leukemia (ETP-ALL)

Abstract No.: 2748

Dr. Huafeng Wang:Our proteomics analysis of ETP-ALL, T-ALL, AML, and healthy donor samples revealed distinctive characteristics of ETP-ALL. Specifically, oxidative phosphorylation (OxPhos) is significantly impaired, primarily due to reduced cytochrome c oxidase and ubiquinone reductase activity. Comprehensive analyses of transcription, translation, enzyme activity, and pathway flux corroborate these findings. Functional assays demonstrated mitochondrial respiration deficits and membrane potential loss in ETP-ALL compared to AML and T-ALL. Restoring OxPhos induces apoptosis and differentiation in ETP-ALL cells, validated in independent patient cohorts. These findings highlight unique proteomic and metabolic features in ETP-ALL, offering new insights into diagnostic standards and potential therapeutic interventions.

Study 4: Impact of Therapeutic Regimens on Prognosis in CEBPAbZIP-inf Mutant AML

Abstract No.: 4274

Dr. Huafeng Wang::This retrospective study analyzed the clinical characteristics, co-mutation profiles, and induction therapy outcomes in 103 patients with CEBPAbZIP-inf AML. Patients underwent one of three induction regimens: intensive chemotherapy (IC, “7+3”), venetoclax with hypomethylating agents (VEN+HMA), or venetoclax with intensified chemotherapy (VEN+IC). The CRc rates for a single cycle were 79.55%, 80%, and 96.3%, respectively, with relapse rates of 31.4%, 50%, and 34.6%. Survival analysis revealed no significant differences in overall survival (OS) or event-free survival (EFS) across the three cohorts, regardless of whether patients were ≤60 or >60 years old. These findings suggest that the choice of induction therapy (IC, VEN+HMA, or VEN+IC) has no significant impact on CRc rates or prognosis in CEBPAbZIP-inf AML patients.

About Dr. Huafeng Wang

• Current Positions: Deputy Director, Department of Hematology, First Affiliated Hospital, Zhejiang University School of Medicine Associate Professor / Associate Chief Physician / PhD Supervisor / Specially Appointed Research Fellow
• Education and Training: Postdoctoral Fellow, City of Hope National Medical Center, USA Visiting Scholar, Brown University, USA, and Royal Free Hospital, UK
• Professional Recognition: Selected as a Rising Star in the Medical Field under the Zhejiang Provincial 551 Talent Plan Member, Targeted Therapy Committee of the Chinese Women Physicians Association Member, Youth Committee of the Hematology Translational Committee, Chinese Anti-Cancer Association Secretary, Hematology Division of the Zhejiang Medical Association Member, Leading Innovation and Entrepreneurship Team in Zhejiang Province
• Academic Achievements: Principal investigator of several National Natural Science Foundation and provincial/ministerial key projects Published over 20 papers as first or corresponding author in journals such as Lancet Haematology, Advanced Science, Leukemia, American Journal of Hematology, and Blood Cancer Journal Delivered multiple oral presentations and abstract reports at international conferences, receiving five ASH Abstract Achievement Awards
• Awards: Second Prize, Zhejiang Provincial Science and Technology Progress Award