Insights on Metabolic Reprogramming and Its Therapeutic Potential in Acute Leukemia

Abstract

Acute leukemias, classified as acute myeloid leukemia and acute lymphoblastic leukemia, represent the most prevalent hematologic tumors in adolescent and young adults. In recent years, new challenges have emerged in order to improve the clinical effectiveness of therapies already in use and reduce their side effects. In particular, in this scenario, metabolic reprogramming plays a key role in tumorigenesis and prognosis, and it contributes to the treatment outcome of acute leukemia. This review summarizes the latest findings regarding the most relevant metabolic pathways contributing to the continuous growth, redox homeostasis, and drug resistance of leukemia cells. We describe the main metabolic deregulations in acute leukemia and evidence vulnerabilities that could be exploited for targeted therapy.

Synergistic Effects of Venetoclax and Daratumumab on Antibody-Dependent Cell-Mediated Natural Killer Cytotoxicity in Multiple Myeloma

“…The number of NK cells rapidly decreased in both the bone marrow and peripheral blood after daratumumab monotherapy [ 18 ]. This reduction in NK cells results in cytotoxicity among neighboring NK cells (NK cell fratricide) [ 19 ]. NK cells with low or no CD38 expression were resistant to their own cytotoxicity induced by daratumumab in an experiment using the peripheral blood and bone marrow of MM patients or healthy donors [ 19 ].…”

“…This reduction in NK cells results in cytotoxicity among neighboring NK cells (NK cell fratricide) [ 19 ]. NK cells with low or no CD38 expression were resistant to their own cytotoxicity induced by daratumumab in an experiment using the peripheral blood and bone marrow of MM patients or healthy donors [ 19 ]. Indeed, these cells demonstrated superior ADCC activity induced by daratumumab than NK cells presenting higher CD38 expression levels [ 19 , 20 ].…”

“…NK cells with low or no CD38 expression were resistant to their own cytotoxicity induced by daratumumab in an experiment using the peripheral blood and bone marrow of MM patients or healthy donors [ 19 ]. Indeed, these cells demonstrated superior ADCC activity induced by daratumumab than NK cells presenting higher CD38 expression levels [ 19 , 20 ]. Whether CD38 expression is correlated with the therapeutic response to a combination therapy of venetoclax and daratumumab remains to be evaluated.…”

The Emerging Roles of LINC00665 in Human Cancers

“…Leukemia is a heterogeneous hematological malignancy caused by uncontrolled neoplastic proliferation of undifferentiated or partially differentiated hematopoietic cells ( Nabavizadeh et al, 2016 ). Acute leukemia is divided into acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) and is the most common hematological tumor in young people ( Di Martino et al, 2021 ). It is crucial to uncover the pathogenesis of acute leukemia and explore novel strategies for acute leukemia treatment.…”

Metabolic Reprogramming and Cell Adhesion in Acute Leukemia Adaptation to the CNS Niche

“…The impact of specific genetic lesions (e.g., MLL rearrangements, BCR-ABL), CNS niche, chemokines, cytokines, and growth factors in driving leukemic cells to the CNS and meninges has been extensively reviewed in (Heidari et al, 2016;Gossai and Gordon, 2017;Piovan et al, 2018;Zhou et al, 2019;Lenk et al, 2020;Whiteley et al, 2021). The roles of metabolic reprogramming and cell adhesion in leukemia development and progression have also been discussed elsewhere (Heath et al, 2019;Rashkovan and Ferrando, 2019;Windisch et al, 2019;Härzschel et al, 2020;Scharff et al, 2020a;Di Martino et al, 2021). However, how metabolic reprograming and cell adhesion regulate leukemic cell infiltration to the CNS remains unclear.…”