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

Abstract

Acute myeloid leukemia (AML) is a highly heterogeneous hematologic neoplasm with poor survival outcomes. However, the routine clinical features are not sufficient to accurately predict the prognosis of AML. The expression of hypoxia-related genes was associated with survival outcomes of a variety of hematologic and lymphoid neoplasms. We established an 18-gene signature-based hypoxia-related prognosis model (HPM) and a complex model that consisted of the HPM and clinical risk factors using machine learning methods. Both two models were able to effectively predict the survival of AML patients, which might contribute to improving risk classification. Differentially expressed genes analysis, Gene Ontology (GO) categories, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to reveal the underlying functions and pathways implicated in AML development. To explore hypoxia-related changes in the bone marrow immune microenvironment, we used CIBERSORT to calculate and compare the proportion of 22 immune cells between the two groups with high and low hypoxia-risk scores. Enrichment analysis and immune cell composition analysis indicated that the biological processes and molecular functions of drug metabolism, angiogenesis, and immune cell infiltration of bone marrow play a role in the occurrence and development of AML, which might help us to evaluate several hypoxia-related metabolic and immune targets for AML therapy.

Endocan in Acute Leukemia: Current Knowledge and Future Perspectives

“…The acute leukemias are bone marrow disorders and endothelial, immunocompetent/inflammatory, and leukemic cells form an interactive network in the bone marrow microenvironment (Figure 2) [10][11][12][66][67][68][69][70][71]. Endocan is released by the endothelial cell and is both regulated by and is a regulator of inflammatory and leukemic cells.…”

“…Local bone marrow infiltration of immunocompetent/inflammatory cells that facilitates leukemic hematopoiesis (e.g., myeloid-derived suppressor cells/MDSC, various T cell subsets, NK cells) has also been described especially in AML [67,68,70,71], and, in particular, the local recruitment of macrophages with modulation of their polarization seems to be an important leukemia-supporting mechanism [68]. The local bone marrow hypoxia [69] and aging of myeloid cells [71] seems to further strengthen the leukemia-facilitating effects of immunocompetent/inflammatory cells.…”