This study investigates how metabolism in cancer and immune cells shapes the bone marrow environment, influences therapy resistance, and affects outcomes in hematological malignancies.

Hematological malignancies, such as acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and myelofibrosis, are aggressive cancers of the blood and immune system. While chemotherapy is commonly used, allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only curative option for many patients. Allo-HSCT relies on donor immune cells, particularly T cells, to eliminate residual malignant cells, but relapse occurs in a significant proportion of patients, underscoring the need for improved therapeutic strategies.

Recent research has highlighted the critical role of cellular metabolism in both cancer cell survival and immune cell function. AML cells, for example, rely on mitochondrial respiration, while immune cells are sensitive to metabolic changes in the bone marrow microenvironment. These metabolic interactions may influence disease progression, therapy resistance, and immune-mediated anti-tumor responses, yet they remain poorly understood.

The primary goal of this study is to investigate how cancer and immune cell metabolism shapes the bone marrow environment and influences treatment outcomes in patients with hematological malignancies. By performing detailed metabolic profiling of malignant cells, immune cells, and extracellular metabolites across disease stages and treatment time points, the study aims to identify key metabolic pathways and interactions that could serve as targets for novel therapies and guide personalized treatment approaches.

This research is expected to deepen the understanding of metabolic mechanisms underlying hematological cancers and allo-HSCT outcomes, potentially leading to improved strategies to enhance anti-tumor immunity, prevent relapse, and optimize patient-specific therapy.

Inclusion Criteria:

• age > 18 years,
• signed written informed consent
• For participants with hematological cancers: diagnosis of MDS, AML, ALL, PMF or post-ET/PV MF

Exclusion Criteria:

• pregnant or lactating women,
• inability to give consent,
• active malignant disease (other than MDS, AML, ALL, PMF or post-ET/PV MF in the last 3 - years prior to study inclusion).
• For healthy donors: previous or current hematological disease, previous or current other malignant disease,

Patients with hematological cancers: Adults (≥18 years) with MDS, AML, ALL, or primary/secondary myelofibrosis from whom blood and bone marrow samples will be collected during the disease course.

Healthy donors: Adults (≥18 years) donating hematopoietic stem cells for allogeneic transplantation, providing peripheral blood or bone marrow samples as a source of healthy stem cells.