Angiogenesis in acute myeloid leukemia

Abstract

Angiogenesis is a word that refers to new blood vessel formation, and this process is of fundamental importance for physiological development and tissue homeostasis, as well as the genesis of several diseases, including tumors. Thus, studies carried out in the last years have shown that angiogenesis is essential for the growth of many solid tumors. Angiogenesis is also important for the growth of many hematological malignancies, including acute myeloid leukemia (AML). Endothelial cells are essential constituents of the bone marrow vascular niches, structures essential for the survival and maintenance of normal hematopoietic stem/progenitor cells. Bone marrow endothelial cells play an essential role in leukemia development and there is growing evidence that a targeting of both leukemic and endothelial cells of the leukemic vascular niche may improve the efficacy of antileukemic therapies. Bone marrow angiogenesis is frequently increased in AML, is morphologically evidenced as increased microvascular density, and is typically associated with some AML subtypes. The molecular mechanisms underlying the increased angiogenesis in some AML subtypes have been defined. In conclusion, a better understanding of angiogenesis as well as the fundamental interactions between bone marrow endothelial cells and leukemic stem cells may contribute to improve antileukemia treatments.

Harnessing upregulated E-selectin while enhancing SDF-1α sensing redirects infused NK cells to the AML-perturbed bone marrow

“…While E-selectin is constitutively expressed on the endothelial cells of BM and skin [ 21 , 22 ], stress conditions like cancer can induce E-selectin upregulation [ 9 , 10 ]. Moreover, this is associated with angiogenesis and increased microvessel density [ 30 , 34 – 36 ] that together with increased E-selectin expression is reported important for retention of leukemic stem cells in the BM [ 34 ]. In fact, the interaction between tumor cells and selectins has been proposed to positively correlate with disease development and is associated with metastasization [ 37 ].…”

Establishment of Prognosis Model in Acute Myeloid Leukemia Based on Hypoxia Microenvironment, and Exploration of Hypoxia-Related Mechanisms

“…Angiogenesis, which was particularly important for tumor survival in the hypoxic condition ( Hanahan and Weinberg, 2011 ), was significantly enriched in the upregulated genes for the high-risk group. Although there are few studies about angiogenesis in hematological malignancy, BM angiogenesis in AML patients has been observed and may play a role in the pathogenesis ( Hussong et al, 2000 ; Padro et al, 2000 ; Testa et al, 2020 ). BM microvessel density of AML patients is higher than that of healthy individuals at the time of diagnosis and decreases after remission ( Padro et al, 2000 ; Song et al, 2015 ).…”