Hypoxia-Inducible Factor1-Α (HIF1α) and Vascular Endothelial Growth Factor-A (VEGF-A) Expression in De Novo AML Patients

Jabari, Mohammad; Farsani, Mehdi Allahbakhshian; Salari, Sina; Hamidpour, Mohsen; Amiri, Vahid; Mohammadi, Mohammad Hossein

doi:10.31557/apjcp.2019.20.3.705

Cited by 24 publications

(20 citation statements)

References 36 publications

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“…Statistical significance was determined via one-way ANOVA, two-way ANOVA, Tukey's multiple comparisons test or unpaired Student's t-test. Pearson's χ 2 test was used to analyze the relationships between PD-L1 and glycolysis-associated genes.…”

Section: Cell Apoptosis Proliferation and Cell Cycle Detectionmentioning

confidence: 99%

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High PD‑L1 expression drives glycolysis via an Akt/mTOR/HIF‑1α axis in acute myeloid leukemia

Xing

Han

et al. 2020

Oncol Rep

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Acute myeloid leukemia (AML) is a hematological malignancy derived from immature myeloid cells, which have the characteristics of abnormal proliferation and differentiation. Glycolysis has been a popular topic of research in recent years, with increasing uptake and consumption of glucose. The present study aimed to investigate the glycolysis of tumor cells in patients with AML; in particular, how programmed cell death 1 ligand 1 (PD-L1) regulates tumor cells glycolysis using real time PCR (RT-PCR), western blotting and flow cytometry. PD-L1 high expression predicted poor outcome in patients with AML in the public database Gene Expression Profiling Interactive Analysis. PD-L1 expression was decreased in the samples from patients with AML with complete remission compared to that in patients with relapsed or refractory AML. In AML cell lines, glycolysis-associated genes ALDOA, PGK1, LDHA and HK2 were highly expressed in a PD-L1 high-expressed cell line. Overexpressed PD-L1 enhanced glucose consumption and the extracellular acidification rate, accompanied by decreased apoptosis and accumulation of cells in the S phase. In contrast, the apoptosis rate of tumor cells and the percentage of cells in the S phase were significantly increased following PD-L1 knockdown in the THP1 cell line. HK2 and LDHA expression decreased after AML tumor cells were treated with Akt inhibitor or rapamycin. In addition, the PD-L1-overexpressed cell line (PD-L1-OV) MOLM-13 exhibited rapid tumor progression. Glycolysis-associated genes were highly expressed in tumor tissues of PD-L1-OV MOLM-13, with increased Ki67. Based on these findings, PD-L1 may be considered as a suitable marker for prognosis and treatment in the clinical setting.

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Section: Cell Apoptosis Proliferation and Cell Cycle Detectionmentioning

confidence: 99%

“…Acute myeloid leukemia (AML) is a complex and common myeloid malignancy, which is accompanied by the abnormal proliferation and differentiation of bone marrow precursor cells in the hematopoietic system (1,2). At the present stage, older adults with this disease have a worse prognosis (3).…”

Section: Introductionmentioning

confidence: 99%

High PD‑L1 expression drives glycolysis via an Akt/mTOR/HIF‑1α axis in acute myeloid leukemia

Xing

Han

et al. 2020

Oncol Rep

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“…In addition to solid tumors, VEGF-A and PlGF play a relevant role in angiogenesis occurring within the bone marrow microenvironment and in acute leukemia spreading at the central nervous system (CNS) site [265][266][267][268][269]. Acute myeloid leukemia (AML) is the most common acute form diagnosed in adults and is characterized by an increased number of immature myeloid cells in the bone marrow, whereas acute lymphocytic leukemia (ALL) is a malignancy of immature lymphocytes that represents 60-74% of all leukemia cases in patients under the age of 20 [270].…”

Section: Tumor Type Metastatic Sites Vegfr-1 Ligands Vegfr-1mentioning

confidence: 99%

Role of VEGFs/VEGFR-1 Signaling and Its Inhibition in Modulating Tumor Invasion: Experimental Evidence in Different Metastatic Cancer Models

Ceci

Atzori

Lacal

et al. 2020

IJMS

175

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The vascular endothelial growth factor (VEGF) family members, VEGF-A, placenta growth factor (PlGF), and to a lesser extent VEGF-B, play an essential role in tumor-associated angiogenesis, tissue infiltration, and metastasis formation. Although VEGF-A can activate both VEGFR-1 and VEGFR-2 membrane receptors, PlGF and VEGF-B exclusively interact with VEGFR-1. Differently from VEGFR-2, which is involved both in physiological and pathological angiogenesis, in the adult VEGFR-1 is required only for pathological angiogenesis. Besides this role in tumor endothelium, ligand-mediated stimulation of VEGFR-1 expressed in tumor cells may directly induce cell chemotaxis and extracellular matrix invasion. Furthermore, VEGFR-1 activation in myeloid progenitors and tumor-associated macrophages favors cancer immune escape through the release of immunosuppressive cytokines. These properties have prompted a number of preclinical and clinical studies to analyze VEGFR-1 involvement in the metastatic process. The aim of the present review is to highlight the contribution of VEGFs/VEGFR-1 signaling in the progression of different tumor types and to provide an overview of the therapeutic approaches targeting VEGFR-1 currently under investigation.

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“…Notably, a correlation between the hypoxia marker HIF1α and VEGF-A has been recently reported. Both are overexpressed in AML cells, but the concentration of HIF1α was significantly higher in AML-M3-derived cells than in other AML cells [ 156 ]. This could be explained by the oncogenic mutation PML-RARA in promyelocytic leukemia (M3) [ 157 ].…”

Section: Dysregulated Leukemic Bone Marrow Microenvironmentmentioning

confidence: 99%

Far from Health: The Bone Marrow Microenvironment in AML, A Leukemia Supportive Shelter

2021

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Acute myeloid leukemia (AML) is the second most common leukemia among children. Although significant progress in AML therapy has been achieved, treatment failure is still associated with poor prognosis, emphasizing the need for novel, innovative therapeutic approaches. To address this major obstacle, extensive knowledge about leukemogenesis and the complex interplay between leukemic cells and their microenvironment is required. The tremendous role of this bone marrow microenvironment in providing a supportive and protective shelter for leukemic cells, leading to disease development, progression, and relapse, has been emphasized by recent research. It has been revealed that the interplay between leukemic cells and surrounding cellular as well as non-cellular components is critical in the process of leukemogenesis. In this review, we provide a comprehensive overview of recently gained knowledge about the importance of the microenvironment in AML whilst focusing on promising future therapeutic targets. In this context, we describe ongoing clinical trials and future challenges for the development of targeted therapies for AML.

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Hypoxia-Inducible Factor1-Α (HIF1α) and Vascular Endothelial Growth Factor-A (VEGF-A) Expression in De Novo AML Patients

Cited by 24 publications

References 36 publications

High PD‑L1 expression drives glycolysis via an Akt/mTOR/HIF‑1α axis in acute myeloid leukemia

High PD‑L1 expression drives glycolysis via an Akt/mTOR/HIF‑1α axis in acute myeloid leukemia

Role of VEGFs/VEGFR-1 Signaling and Its Inhibition in Modulating Tumor Invasion: Experimental Evidence in Different Metastatic Cancer Models

Far from Health: The Bone Marrow Microenvironment in AML, A Leukemia Supportive Shelter

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