Metabolism Reprogramming in Hematological Malignancies

Hematological malignancies represent a heterogeneous group of disorders arising from the transformation of hematopoietic cells or mature elements. Over the past two decades, substantial advances in molecular oncology have fundamentally reshaped our understanding of their pathogenesis. Among the most compelling paradigm shifts is the recognition that metabolic reprogramming is not merely a secondary consequence of malignant transformation, but rather a central and active driver of tumor initiation, progression, immune evasion, and therapeutic resistance.Cancer cells within the hematological compartment exploit a wide spectrum of metabolic adaptations to meet their energetic and biosynthetic demands. These include, but are not limited to, aerobic glycolysis (the Warburg effect), oxidative phosphorylation (OXPHOS) dependency, glutamine addiction, lipid metabolism rewiring, one-carbon metabolism alterations, and amino acid catabolism. Furthermore, oncometabolites — aberrant metabolic intermediates such as 2-hydroxyglutarate produced by mutant IDH1/2 enzymes — have been shown to directly interfere with epigenetic regulation, further intertwining metabolism with gene expression control. The bone marrow microenvironment adds an additional layer of complexity, providing metabolic niches that cancer cells actively co-opt to sustain survival and resist therapeutic pressure.Importantly, the increasing availability of high-resolution multi-omics technologies — including metabolomics, proteomics, transcriptomics, and single-cell analyses — has opened unprecedented opportunities to dissect the metabolic heterogeneity of hematological malignancies at both the bulk and single-cell levels. These advances have simultaneously unveiled novel vulnerabilities that hold significant translational potential.Despite remarkable progress, a comprehensive and integrated understanding of metabolic reprogramming across the full spectrum of hematological malignancies remains elusive. Critical questions persist regarding the mechanisms by which specific metabolic adaptations confer clonal advantage, the extent to which metabolic phenotypes predict clinical behavior and response to therapy, and how the tumor microenvironment modulates or is modulated by malignant cell metabolism. This Research Topic aims to consolidate current knowledge, highlight emerging concepts, and identify actionable metabolic vulnerabilities in hematological malignancies. By gathering original research articles, systematic reviews, and perspectives from international experts, we intend to provide a timely and authoritative resource that bridges fundamental metabolic biology with clinical and translational oncology, ultimately fostering the development of novel, metabolism-targeted therapeutic strategies for patients affected by these diseases. We welcome contributions addressing, but not limited to, the following specific themes:• Warburg effect and glycolytic reprogramming in acute leukemias, lymphomas, and plasma cell neoplasms, including mechanistic underpinnings and therapeutic targeting• Mitochondrial metabolism and OXPHOS dependency in hematological malignancies, with emphasis on metabolic plasticity and resistance to BCL-2 inhibitors and other targeted agents• Oncometabolites and epigenetic crosstalk: the role of IDH1/2 mutations, 2-hydroxyglutarate, and related metabolic alterations in leukemogenesis and lymphomagenesis• Glutamine, amino acid, and lipid metabolism as drivers of proliferation and survival in hematological tumors• One-carbon metabolism and nucleotide biosynthesis in the context of clonal hematopoiesis, MDS, and acute leukemias• Metabolic reprogramming in the bone marrow and lymphoid tissue microenvironments, including metabolic competition between malignant cells, stromal cells, and immune effectors• Metabolic determinants of drug resistance, including resistance to conventional chemotherapy, targeted therapies, and immunotherapies• Single-cell and spatial metabolomics approaches applied to hematological malignancies• Novel metabolism-targeting therapeutic strategies, including small molecule inhibitors of metabolic enzymes, dietary interventions, and combination approaches• Metabolic biomarkers for diagnosis, prognosis, and treatment monitoring in hematological cancers• Comparative and epidemiological perspectives on metabolic reprogramming in hematological malignancies across diverse geographic and ethnic populationsPlease note: Manuscripts consisting solely of bioinformatics, computational analysis, or predictions of public databases which are not accompanied by validation (independent clinical or patient cohort, or biological validation in vitro or in vivo, which are not based on public databases) are not suitable for publication in this journal. Topic editors: Pier Paolo Piccaluga, Ming Chen Source: https://www.frontiersin.org/research-topics/79928/metabolism-reprogramming-in-hematological-malignancies