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Indian Journal of Hematology and Blood Transfusion
Published in: Indian Journal of Hematology and Blood Transfusion 2/2021

01-04-2021 | Acute Myeloid Leukemia | Original Article

Evaluation of LKB1 and Serine-Glycine Metabolism Pathway Genes (SHMT1 and GLDC) Expression in AML

Authors: Fateme Mezginejad, Mohammad Hossein Mohammadi, Parinaz khadem, Mehdi Allahbakhshian Farsani

Published in: Indian Journal of Hematology and Blood Transfusion | Issue 2/2021

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Abstract

LKB1 is a significant tumor suppressor and epigenetic regulator playing a vital role in different types of cancers. SHMT1 and GLDC are two critical genes of the epigenetic pathway influenced by LKB1. As epigenetic is the major cause of AML pathogenesis, this study aimed at investigating LKB1, SHMT1, and GLDC gene expression levels in acute myeloid leukemia patients. The present study was conducted on LKB1, SHMT1, and GLDC gene expression levels in 60 de novo AML samples and 30 normal controls using real-time RT-PCR. The results showed that LKB1 and SHMT1 have respectively a significantly lower (P < 0.05) and higher (P < 0.05) expression level than that of normal controls. Furthermore, the correlation between LKB1 with SHMT1 and GLDC was significant and positive (P value: 0.015, r: 0.299). Positive findings confirm that metabolic pathways alongside the LKB1 association drive the epigenetic axis and its substrate production. Therefore, it can be concluded that the newly-discovered pathway in the pathogenesis of this disease provides new insights into the design of therapeutic targets.
Literature
1.
Nezhad HA, Mohammadi MH, Khosravi MR, Salari S, Hajifathali A, Farsani MA (2018) The evaluation of p21 and p27 expression in HLA-DR negative AML patients. Middle East J Fam Med 7(10):253
2.
Salarpour F, Goudarzipour K, Mohammadi MH, Ahmadzadeh A, Faraahi S, Allahbakhshian A et al (2018) Evaluation of growth factor independence 1 expression in patients with de novo acute myeloid leukemia. J Cancer Res Ther 16(1):23
3.
Amiri V, Mohammadi M, Farsani MRK, Gharehbaghian A, Hajifathali A, Khazaei Z et al (2018) Evaluation of UHRF1 and P16INK4A expression levels in newly diagnosed AML patients. Biomed Res Ther 5(9):2658–2663CrossRef
4.
Eriksson A, Lennartsson A, Lehmann S (2015) Epigenetic aberrations in acute myeloid leukemia: early key events during leukemogenesis. Exp Hematol 43(8):609–624CrossRef
5.
Gan R-Y, Li H-B (2014) Recent progress on liver kinase B1 (LKB1): expression, regulation, downstream signaling and cancer suppressive function. Int J Mol Sci 15(9):16698–16718CrossRef
6.
Green AS, Chapuis N, Lacombe C, Mayeux P, Bouscary D, Tamburini J (2011) LKB1/AMPK/mTOR signaling pathway in hematological malignancies: from metabolism to cancer cell biology. Cell Cycle 10(13):2115–2120CrossRef
7.
Zhou W, Marcus AI, Vertino PM (2013) Dysregulation of mTOR activity through LKB1 inactivation. Chin J Cancer 32(8):427CrossRef
8.
Kottakis F, Nicolay BN, Roumane A, Karnik R, Gu H, Nagle JM et al (2016) LKB1 loss links serine metabolism to DNA methylation and tumorigenesis. Nature 539(7629):390CrossRef
9.
Mentch SJ, Mehrmohamadi M, Huang L, Liu X, Gupta D, Mattocks D et al (2015) Histone methylation dynamics and gene regulation occur through the sensing of one-carbon metabolism. Cell Metab 22(5):861–873CrossRef
10.
Schoofs T, Berdel W, Müller-Tidow C (2014) Origins of aberrant DNA methylation in acute myeloid leukemia. Leukemia 28(1):1CrossRef
11.
Wang Y-W, Zhang S-D, Xue W-J, Zhu M-L, Zheng L-Z (2015) SHMT1 C1420T polymorphism contributes to the risk of non-Hodgkin lymphoma: evidence from 7309 patients. Chin J Cancer 34(3):60CrossRef
12.
Zhao T, Shen L, Zhang X, Gu D, Zhang Q, Huo X et al (2015) Clinical significance of SHMT1 rs1979277 polymorphism in Asian solid tumors: evidence from a meta-analysis. Genet Mol Res 14:5602–5614CrossRef
13.
Noh S, Kim DH, Jung WH, Koo JS (2014) Expression levels of serine/glycine metabolism-related proteins in triple negative breast cancer tissues. Tumor Biol 35(5):4457–4468CrossRef
14.
Li X, Cui C, Guo Y, Yang G (2015) Glycine decarboxylase expression increased in p53-Mutated B cell lymphoma mice. Oncol Res Treat 38(11):586–589CrossRef
15.
Toyota M, Kopecky KJ, Toyota M-O, Jair K-W, Willman CL, Issa J-PJ (2001) Methylation profiling in acute myeloid leukemia. Blood 97(9):2823–2829CrossRef
16.
Green AS, Chapuis N, Maciel TT, Willems L, Lambert M, Arnoult C et al (2010) The LKB1/AMPK signaling pathway has tumor suppressor activity in acute myeloid leukemia through the repression of mTOR-dependent oncogenic mRNA translation. Blood 2010:blood-2010-02-269837
17.
Zhang W, Ding Y, Zhang C, Lu Q, Liu Z, Coughlan K et al (2017) Deletion of endothelial cell-specific liver kinase B1 increases angiogenesis and tumor growth via vascular endothelial growth factor. Oncogene 36(30):4277CrossRef
18.
Ma L-G, Bian S-B, Cui J-X, Xi H-Q, Zhang K-C, Qin H-Z et al (2016) LKB1 inhibits the proliferation of gastric cancer cells by suppressing the nuclear translocation of Yap and β-catenin. Int J Mol Med 37(4):1039–1048CrossRef
19.
Yang Y, Takeuchi S, Hofmann WK, Ikezoe T, van Dongen JJ, Szczepański T et al (2006) Aberrant methylation in promoter-associated CpG islands of multiple genes in acute lymphoblastic leukemia. Leuk Res 30(1):98–102CrossRef
20.
Paone A, Marani M, Fiascarelli A, Rinaldo S, Giardina G, Contestabile R et al (2014) SHMT1 knockdown induces apoptosis in lung cancer cells by causing uracil misincorporation. Cell Death Dis 5(11):e1525CrossRef
21.
Go MK, Zhang WC, Lim B, Yew WS (2014) Glycine decarboxylase is an unusual amino acid decarboxylase involved in tumorigenesis. Biochemistry 53(5):947–956CrossRef
Metadata
Title
Evaluation of LKB1 and Serine-Glycine Metabolism Pathway Genes (SHMT1 and GLDC) Expression in AML
Authors
Fateme Mezginejad
Mohammad Hossein Mohammadi
Parinaz khadem
Mehdi Allahbakhshian Farsani
Publication date
01-04-2021
Publisher
Springer India
Published in
Indian Journal of Hematology and Blood Transfusion / Issue 2/2021
Print ISSN: 0971-4502
Electronic ISSN: 0974-0449
DOI
https://doi.org/10.1007/s12288-020-01329-1

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