Metabolic pathways have been implicated in multiple biological processes, including cell fate decision, proliferation, and differentiation in several hematopoietic and immune cell types. Targeting specific metabolic pathways such as glycolysis, fatty acid oxidation by specific drugs is currently used in the clinic for very diverse types of diseases. The broad applications include cancer and leukemia, but also gene and cell therapy to protect/maintain the cell’s biological properties ex vivo. However, additional detailed studies on metabolism are the prerequisite for identifying less toxic and more efficient therapies.
All immune cells are generated from hematopoietic stem cells (HSCs), which reside at the top of a multi-step process called hematopoiesis. HSCs possess unique self-renewal capacity, multilineage potential and are also characterized by their unique metabolic state. Recent work has suggested that the switch of the metabolic state dictates the hematopoietic differentiation process at several steps during hematopoiesis. Indeed, metabolic state changes have been shown to have a role in several processes, including HSC fate decision and progenitor commitment. Recently, the metabolic regulation of the bone marrow microenvironment has been involved in shaping normal and malignant hematopoiesis. Finally, dysregulation of various metabolic pathways has also been involved in leukemic transformation, propagation, and drug resistance.
Soluble final and/or intermediate products, as well as wastes such as reactive oxygen species (ROS) of metabolic processes, are used at the physiological level to regulate key proteins of signaling pathways involved in cell differentiation, proliferation, etc. ROS are known to regulate protein function through their oxidation. The deregulation of these soluble mediators can give rise to abnormal fate decisions. Indeed, the deregulation of ROS levels pushes toward HSC differentiation at the expense of HSC self-renewal. In some cases, some abnormal intermediate products are produced and could also drive leukemic transformation and BM failure; this was described for IDH1 and IDH2 mutants that led to the production of 2-hydroxyglutarate (2-HG), known to participate in leukemogenesis, instead of a Ketoglutarate (a-KG). Recently, metabolic mediators have been used in vitro in preclinical studies to improve protocols of cell therapy and HSC manipulation in vitro/ex vivo.
Here, we aim to address the multiple facets of metabolism in HSC biology, hematopoietic specification, commitment, and differentiation as well as their involvement in leukemic transformation and drug resistance.
This Research Topic aims to gather Reviews (Mini Reviews, Reviews, Opinions) as well as novel Original Research articles focusing on the involvement of metabolic processes in HSC biology, hematopoietic differentiation and maturation, HSC expansion, and leukemic transformation. Metabolic processes will act on these basic functions through soluble mediators such as final and/or intermediate metabolic products but also metabolic wastes (ROS) released from each round of metabolic loop. We will be happy to welcome contribution from colleagues from diverse fields addressing the following subtopics:
1. Involvement of metabolism in HSC fate decisions, commitment, and differentiation and lymphopoiesis and myelopoiesis,
2. Involvement of metabolism in leukemic transformation and drug resistance,
3. Consequences of metabolic changes in bone marrow microenvironment on normal and leukemic hematopoietic cells
4. Deregulation of metabolic pathways in multiple myeloma, lymphoma, leukemia, and other blood malignancies.
5. Clinical application of the modulation of metabolic pathways: targeting metabolic pathways by the use of inhibitors, in normal and pathologic context, to either encounter leukemia resistance to regular treatments or, in the case of gene and/or cell therapy, to expand/maintain HSC number ex vivo.
Metabolic pathways have been implicated in multiple biological processes, including cell fate decision, proliferation, and differentiation in several hematopoietic and immune cell types. Targeting specific metabolic pathways such as glycolysis, fatty acid oxidation by specific drugs is currently used in the clinic for very diverse types of diseases. The broad applications include cancer and leukemia, but also gene and cell therapy to protect/maintain the cell’s biological properties ex vivo. However, additional detailed studies on metabolism are the prerequisite for identifying less toxic and more efficient therapies.
All immune cells are generated from hematopoietic stem cells (HSCs), which reside at the top of a multi-step process called hematopoiesis. HSCs possess unique self-renewal capacity, multilineage potential and are also characterized by their unique metabolic state. Recent work has suggested that the switch of the metabolic state dictates the hematopoietic differentiation process at several steps during hematopoiesis. Indeed, metabolic state changes have been shown to have a role in several processes, including HSC fate decision and progenitor commitment. Recently, the metabolic regulation of the bone marrow microenvironment has been involved in shaping normal and malignant hematopoiesis. Finally, dysregulation of various metabolic pathways has also been involved in leukemic transformation, propagation, and drug resistance.
Soluble final and/or intermediate products, as well as wastes such as reactive oxygen species (ROS) of metabolic processes, are used at the physiological level to regulate key proteins of signaling pathways involved in cell differentiation, proliferation, etc. ROS are known to regulate protein function through their oxidation. The deregulation of these soluble mediators can give rise to abnormal fate decisions. Indeed, the deregulation of ROS levels pushes toward HSC differentiation at the expense of HSC self-renewal. In some cases, some abnormal intermediate products are produced and could also drive leukemic transformation and BM failure; this was described for IDH1 and IDH2 mutants that led to the production of 2-hydroxyglutarate (2-HG), known to participate in leukemogenesis, instead of a Ketoglutarate (a-KG). Recently, metabolic mediators have been used in vitro in preclinical studies to improve protocols of cell therapy and HSC manipulation in vitro/ex vivo.
Here, we aim to address the multiple facets of metabolism in HSC biology, hematopoietic specification, commitment, and differentiation as well as their involvement in leukemic transformation and drug resistance.
This Research Topic aims to gather Reviews (Mini Reviews, Reviews, Opinions) as well as novel Original Research articles focusing on the involvement of metabolic processes in HSC biology, hematopoietic differentiation and maturation, HSC expansion, and leukemic transformation. Metabolic processes will act on these basic functions through soluble mediators such as final and/or intermediate metabolic products but also metabolic wastes (ROS) released from each round of metabolic loop. We will be happy to welcome contribution from colleagues from diverse fields addressing the following subtopics:
1. Involvement of metabolism in HSC fate decisions, commitment, and differentiation and lymphopoiesis and myelopoiesis,
2. Involvement of metabolism in leukemic transformation and drug resistance,
3. Consequences of metabolic changes in bone marrow microenvironment on normal and leukemic hematopoietic cells
4. Deregulation of metabolic pathways in multiple myeloma, lymphoma, leukemia, and other blood malignancies.
5. Clinical application of the modulation of metabolic pathways: targeting metabolic pathways by the use of inhibitors, in normal and pathologic context, to either encounter leukemia resistance to regular treatments or, in the case of gene and/or cell therapy, to expand/maintain HSC number ex vivo.