Document Type : Original Article
Authors
- Parinaz Khadem 1
- Ali Keshavarz 1
- Mohammad Hossein Mohammadi 1, 2
- Fateme Mezginejad 3
- Mehdi Allahbakhshian Farsani 1
1 Department of Hematology and Blood Banking, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
2 Hematopoietic Stem Cell Transplantation (HSCT) Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
3 Cellular and Molecular Research Center, Birjand University of Medical Sciences, Birjand, Iran
Abstract
Background: Acute myeloid leukemia (AML) is characterized by the uncontrolled proliferation of malignant cells, which rely on various metabolic pathways to sustain their survival and growth. In this regard, the serine synthesis pathway (SSP) is critically involved in generating biological macromolecules and oncogenic metabolites that are fundamental in tumor growth and proliferation. As a result, this study aimed to assess the expression of SSP-related genes, including Phosphoserine aminotransferase (PSAT1), phosphoglycerate dehydrogenase (PHGDH), and 1-3-phosphoserine phosphatase (PSPH) in AML patients.
Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to assess the expression of PHGDH, PSAT1, and PSPH genes in samples from 60 newly diagnosed AML patients and 10 healthy controls.
Results: Our investigation revealed decreased expression of PSAT1 and PSPH in AML patients compared to controls (P = 0.002, P = 0.026, respectively). However, no significant change was observed in PHGDH expression. Moreover, positive correlations were identified between the expression levels of PHGDH and PSAT1 (r = 0.488, P = 0.0002), PHGDH and PSPH (r = 0.379, P = 0.007), and PSAT1 and PSPH (r = 0.331, P = 0.01) in AML patients.
Conclusion: Although malignant cells are exposed to serine restriction, it seems that SSP up-regulation is not beneficial to myeloid blasts. This may be justified by applying alternative sources to compensate required serine for these cells. More investigations can shed light on the importance of alternative sources as therapeutic targets in AML patients.
Keywords
- Serine biosynthesis
- Phosphoglycerate dehydrogenase
- Phosphoserine aminotransferase
- Phosphoserine phosphatase
Main Subjects
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