Abstract
Despite recent advancements in the treatment of hematologic malignancies and the emergence of newer and more sophisticated therapeutic approaches such as immunotherapy, long-term overall survival remains unsatisfactory. Metabolic alteration, as an important hallmark of cancer cells, not only contributes to the malignant transformation of cells, but also promotes tumor progression and metastasis. As an immune-escape mechanism, the metabolic adaptation of the bone marrow microenvironment and leukemic cells is a major player in the suppression of anti-leukemia immune responses. Therefore, metabolic rewiring in leukemia would provide promising opportunities for newer therapeutic interventions. Several therapeutic agents which affect essential bioenergetic pathways in cancer cells including glycolysis, β-oxidation of fatty acids and Krebs cycle, or anabolic pathways such as lipid biosynthesis and pentose phosphate pathway, are being tested in various types of cancers. So far, numerous preclinical or clinical trial studies using such metabolic agents alone or in combination with other remedies such as immunotherapy are in progress and have demonstrated promising outcomes. In this review, we aim to argue the importance of metabolic alterations and bioenergetic pathways in different types of leukemia and their vital roles in disease development. Designing treatments based on targeting leukemic cells vulnerabilities, particularly in nonresponsive leukemia patients, should be warranted.
Highlights
Hematologic malignancies are heterogeneous disorders caused by the carcinogenic transformation of hematopoietic cells
We summarized the alteration of metabolic events supplementing building blocks and energy for rapid proliferation, drug resistance, self-renewal, etc. during leukemogenesis
The importance of cross-talk between leukemia cells and immunocytes has been highlighted in the text, especially under complicated bone marrow microenvironment (BMM) conditions
Summary
Hematologic malignancies are heterogeneous disorders caused by the carcinogenic transformation of hematopoietic cells. Leukemias are the most common set of these malignancies characterized by rapid and aggressive production of abnormal white blood cells (WBCs) that are not functional and efficient immune cells Metabolic adaptations contribute to cancer cells transformation, and promote tumor progression [5, 6] It seems that metabolic rewiring is a critical implement for leukemic cells so that metabolic properties of these cells can remarkably influence the disease progress and effective response to treatments. Metabolic adaptations in the BMM and leukemic cells have a critical role in the suppression and eradication of anti-leukemia immune responses [10, 11] Regarding these issues, metabolic vulnerabilities in leukemia provide promising opportunities for therapeutic intervention. Designing of treatment based on targeting leukemic cells vulnerabilities, in nonresponsive leukemia patients, is considered
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
