Background:Bone marrow hypoxia can promote leukemia progression in human cases of acute myeloid leukemia (AML). In addition, low oxygen tension is able to regulate the expression of different genes involved in malignancy. In this study, we hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF-A) genes were assessed as principal regulators of hypoxia in do novo AML patients.Methods:Peripheral blood and bone marrow samples were collected from 57 AML patients and 17 normal control subjects with informed consent. Expression of HIF1α and VEGF-A was then evaluated using quantitative real-time PCR (Q-Real time PCR) and data were analyzed with SPSS 16.Result:HIF1α and VEGF-A showed overexpression in AML patients compared to normal controls (P <0.0001 and P<0.005, respectively). The expression level of HIF1α was significantly higher in AML-M3 cases versus AML-non M3 cases. Furthermore, there was a positive correlation between HIF1α and VEGF-A (P <0.0001 and r = 0.497).Conclusion:Adding to the many studies on the role of hypoxia in solid tumors, our data indicate that HIF1a and VEGF-A overexpression also occurs in AML patients. We consider that this is possibly involved in leukemic cell growth and therefore could be a promising target for clinical control.
Multiple factors, including growth factors, are shown to be culprits of cancer outset and persistence. Among growth factors, insulin-like growth factors (IGFs) family are of more importance in the prognosis of blood malignancies. After binding to their corresponding receptor, IGFs initiate PI3K/AKT signaling pathway and increase the translation of intracellular proteins, such as cell division-related proteins. They also stimulate the transcription of cell divisionrelated genes using the Ras-GTP pathway. In addition to organs such as the liver, IGFs are secreted by tumor cells and can cause growth and proliferation of self or tumor cells via autocrine and paracrine methods. Current studies indicate that decreasing the effects of IGF by blocking them, their receptors, or PI3K/AKT pathway using various drugs could help to suppress the division of tumor cells. Here, we delineate the role of the IGF family in hematologic malignancies and their potential mechanisms.
The CCAAT/enhancer binding protein (C/EBP) alpha (CEBPA) and Runt-related transcription factor 1 (RUNX1) genes have been traditionally regarded as two essential genes involved in normal myeloid maturation. Although the link between mutations in these genes and the development of acute myeloid leukemia (AML) has been extensively documented, the ramifications of gene expression dysregulations of CEBPA and RUNX1 has drawn less attention. The present study investigated CEBPA and RUNX1 gene expression levels in 96 primary AML specimens against a normal control group by way of real-time RT-PCR. Our results reveal that CEBPA and RUNX1 gene expression levels were unexpectedly and significantly higher in patients with AML when compared to the levels detected in the normal control group (P < 0.0001). Furthermore, the correlation between CEBPA and RUNX1 was significant and positive (P-value: 0.011, r: 0.257). Our data contradicts the widely established role of CEBPA and RUNX1 in myeloid differentiation, as we saw lower levels of CEBPA and RUNX1 expression to be exhibited in patients with AML. Likely, our data demonstrates that higher levels of CEBPA and RUNX1 expression were closely correlated with reduced myeloid maturation, but this idea needs to approved. It suggests that despite the current established functions of genes involved in cell differentiation, the leukemogenesis process has the capability to transform normal hematopoietic precursors in a manner that may employ the differentiation related gene at the service of malignancy.
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