Metabolic Rewiring and Microenvironmental Interactions in Therapy-Resistant Hematologic Malignancies

In the field of hematology, therapy resistance, relapse, and impaired hematopoietic recovery remain key challenges not only in malignant disorders but also in non-malignant settings such as bone marrow failure syndromes, transplantation, and red blood cell (RBC) pathobiology. Current research highlights the central role of the bone marrow microenvironment as a regulator of both malignant and non-malignant stem and progenitor cell behavior. The intricate interplay between stromal, vascular, and immune signals—including extracellular vesicles, metabolic cues, and redox dynamics—shapes cellular adaptation, survival, quiescence, and lineage commitment.

Mitochondrial function and redox pathways are increasingly recognized as crucial determinants of hematopoietic stem cell fate, erythropoiesis, transplant outcomes, and responses to cellular stress. While significant progress has been made in decoding metabolic rewiring in hematologic diseases, a comprehensive integration of mitochondrial quality control, redox signaling, and microenvironmental influences remains underdeveloped. This creates an exciting opportunity to unify insights across malignancies, regenerative hematology, transplantation, and RBC biology.

This Research Topic aims to establish a robust platform for exploring the convergences between metabolic and redox regulation and the surrounding microenvironment across the hematology spectrum. We seek to uncover molecular mechanisms underlying mitochondrial dynamics, autophagy, ferroptosis, and oxidative adaptation, while also examining how stromal, vascular, and immune niches shape hematopoiesis, erythropoiesis, and malignant progression. The goal is to integrate basic mechanistic understanding with translational perspectives relevant to therapy resistance, bone marrow transplantation, red blood cell physiology, and hematologic recovery.

We welcome contributions that investigate how complex metabolic and microenvironmental interactions influence hematologic cell fate, disease progression, and treatment outcomes. Manuscripts may address— but are not limited to— the following themes:

• Mitochondrial quality control, mitophagy, and autophagy mechanisms in hematologic cells
• Redox metabolism and regulated cell death pathways (e.g., ferroptosis) in leukemia and other hematologic contexts
• Extracellular vesicle–mediated communication within bone marrow niches and during transplantation
• Vascular, stromal, and immune microenvironmental factors shaping hematopoiesis and malignant stem cell survival
• Redox regulation in erythropoiesis and red blood cell biology
• Metabolism-driven therapy resistance, graft function, and transplant biology
• Microenvironmental and metabolic determinants of hematopoietic recovery after stress or conditioning

We encourage submissions spanning mechanistic cellular studies, preclinical modeling, translational or clinical research, systematic reviews, and perspectives aimed at integrating metabolic, microenvironmental, and redox-focused viewpoints across hematology.

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Clinical Trial
• Data Report
• Editorial
• FAIR² Data
• FAIR² DATA Direct Submission
• General Commentary
• Methods
• ... View all formats

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Clinical Trial
• Data Report
• Editorial
• FAIR² Data
• FAIR² DATA Direct Submission
• General Commentary
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Study Protocol
• Systematic Review

Keywords: Leukemia stem cells, Mitochondrial dynamics, Redox biology, Bone marrow microenvironment, Therapy resistance

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.