Abstract
Acute myeloid leukemia (AML) is a clonal disorder characterized by genetic aberrations in myeloid primitive cells (blasts) which lead to their defective maturation/function and their proliferation in the bone marrow (BM) and blood of affected individuals. Current intensive chemotherapy protocols result in complete remission in 50% to 80% of AML patients depending on their age and the AML type involved. While alterations in calcium signaling have been extensively studied in solid tumors, little is known about the role of calcium in most hematologic malignancies, including AML. Our purpose with this review is to raise awareness about this issue and to present (i) the role of calcium signaling in AML cell proliferation and differentiation and in the quiescence of hematopoietic stem cells; (ii) the interplay between mitochondria, metabolism, and oxidative stress; (iii) the effect of the BM microenvironment on AML cell fate; and finally (iv) the mechanism by which chemotherapeutic treatments modify calcium homeostasis in AML cells.
Highlights
Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy at the biological, molecular, and clinical levels
Taking into account the current knowledge of calcium signaling in cancer cells as well as in normal hematopoiesis, our purpose is to shed light on four peculiar topics: (i) the quiescence of these hematopoietic stem cells and AML cell proliferation and differentiation; (ii) the role of mitochondria, metabolism, and oxidative stress; (iii) the effect of the bone marrow (BM) microenvironment on AML cells; and (iv) therapeutic approaches
We here focus on studies that highlight a functional role for Ca2+ channels and downstream intracellular signaling pathways that lead to changes in proliferation and differentiation in acute myeloid leukemia
Summary
Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy at the biological, molecular, and clinical levels. Dysregulated calcium signaling cascades have been shown to result in processes crucial for uncontrolled proliferation and tumorigenesis These processes include gene transcription, regulation of the cell cycle, proliferation, metabolism, apoptosis, autophagy, and cell migration and may affect the development of resistance to cancer therapies [6]. Fukushima et al developed another strategy by which a non-phosphorylatable fluorescent marker allows in vivo discrimination between dormant and active stem cells [9] It shows the implication of calcium concentration in dormancy and that marrow reconstitution by HSC is favored by a high concentration of cytoplasmic calcium. Taking into account the current knowledge of calcium signaling in cancer cells as well as in normal hematopoiesis, our purpose is to shed light on four peculiar topics: (i) the quiescence of these hematopoietic stem cells and AML cell proliferation and differentiation; (ii) the role of mitochondria, metabolism, and oxidative stress; (iii) the effect of the BM microenvironment on AML cells; and (iv) therapeutic approaches
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