Investigating the effect of MAP2K1 gene (MEK1) in MAPK pathway in the induction of adult T-cell leukemia/lymphoma (ATLL)
-
Parastoo Hosseini
,
Abbas Rahimi Foroushani
,
Arezoo Marjani
,
Mahnaz Tavakoli
,
Abdollah Amiri
,
Amin Hosseini
,
Atefeh Bahavar
,
Sayed-Hamidreza Mozhgani
,
Mehdi Norouzi
Abstract
Background and Objectives: HTLV-1 is responsible for two important diseases, HAM/TSP and ATLL. Approximately 10 to 20 million people are infected with HTLV-1 worldwide. Identifying altered genes in different cancers is crucial for finding potential treatment strategies. One of the proteins of the RAS/MAPK signaling pathway is MEK1, which is made from the MAP2K1 gene. The effects of the MAP2K1 gene on the MAPK signaling pathway are not yet fully elucidated. The current study aims to determine the MAP2K1 gene mutations and the level of MAP2K1 gene expression in ATLL patients compared to healthy individuals.
Materials and Methods: Ten ATLL and 10 healthy control individuals were investigated in this study. We used ELISA test to screen anti-HTLV-I antibodies and PCR for confirmation of infection. Then, we extracted total RNA from fresh whole blood, and cDNA was synthesized. The expression levels of the MAP2K1 gene were examined by qRT-PCR, and to check possible mutations in the MAP2K1 gene; all samples were sequenced and analyzed by BioEdite Software.
Results: MAP2K1 gene expression in the ATLL group was significantly higher than in the healthy control (P=0.001). The mutational sequencing analysis showed nucleotide 212 (S→R) change and identification mutations at different nucleotides that were entirely different from the nucleotide mutations defined in the UniProt database.
Conclusion: These results could be a perspective in the prevention, prognosis, and targeted treatment of diseases in which the MAP2K1 gene plays a vital role.
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17. Wang W, Xu C, Wang D, Zhu Y, Zhuang W, Fang M, et al. P70. 05 The Association between MAP2K1 mutation class and clinical features in MAP2K1-mutant East Asian non-small cell lung cancer patients. J Thorac Oncol 2021; 16: S564.
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19. Pourrezaei S, Shadabi S, Gheidishahran M, Rahimiforoushani A, Akhbari M, Tavakoli M, et al. Molecular epidemiology and phylogenetic analysis of human T-lymphotropic virus type 1 in the tax gene and it association with adult t-cell leukemia/lymphoma disorders. Iran J Microbiol 2021; 13: 509-517.
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21. Mozhgani S-H, Jahantigh HR, Rafatpanah H, Valizadeh N, Mohammadi A, Basharkhah S, et al. Interferon lambda family along with HTLV-1 proviral load, tax, and HBZ implicated in the pathogenesis of myelopathy/tropical spastic paraparesis. Neurodegener Dis 2018;18:150-5.
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24. Meysami P, Alavian SM, Monavari SH, Mozhgani SH, Taghizadeh M, Farahani M, et al. Molecular characterization of hepatitis D virus genotypes circulating in Iran. Future Virol 2018;13: 265-273.
25. Soltani S, Mozhgani SH, Siri G, Emadi MS, Foroushani AR, Jazayeri SM, et al. High Expression of Inflammatory Cytokines and Chemokines in Human T-lymphotropic Virus 1-Associated Adult T-cell Leukemia/Lymphoma. Jundishapur J Microbiol 2022; 15(10): e132348.
26. Choi YL, Soda M, Ueno T, Hamada T, Haruta H, Yamato A, et al. Oncogenic MAP2K1 mutations in human epithelial tumors. Carcinogenesis 2012; 33: 956-961.
27. Estep AL, Palmer C, McCormick F, Rauen KA. Mutation analysis of BRAF, MEK1 and MEK2 in 15 ovarian cancer cell lines: implications for therapy. PLoS One 2007; 2(12): e1279.
28. Marks JL, Gong Y, Chitale D, Golas B, McLellan MD, Kasai Y, et al. Novel MEK1 mutation identified by mutational analysis of epidermal growth factor receptor signaling pathway genes in lung adenocarcinoma. Cancer Res 2008; 68: 5524-5528.
29. Bentivegna S, Zheng J, Namsaraev E, Carlton VE, Pavlicek A, Moorhead M, et al. Rapid identification of somatic mutations in colorectal and breast cancer tissues using mismatch repair detection (MRD). Hum Mutat 2008; 29: 441-450.
30. Williams EA, Montesion M, Shah N, Sharaf R, Pavlick DC, Sokol ES, et al. Melanoma with in-frame deletion of MAP2K1: A distinct molecular subtype of cutaneous melanoma mutually exclusive from BRAF, NRAS, and NF1 mutations. Mod Pathol 2020; 33: 2397-2406.
31. Mohammadpour M, Najd Mazhar F, Rajei M, Razi S, Rashidi H, Hassanzdeh M. Melorheostosis in proximal phalanx and metacarpal bone: a short-mid-term follow up. Mod Med Lab J 2022; 5: 56-60.
32. Brown NA, Furtado LV, Betz BL, Kiel MJ, Weigelin HC, Lim MS, et al. High prevalence of somatic MAP2K1 mutations in BRAF V600E–negative Langerhans cell histiocytosis. Blood 2014; 124: 1655-1658.
2. Mohanty S, Harhaj EW. Mechanisms of oncogenesis by HTLV-1 Tax. Pathogens 2020; 9: 543.
3. Miura M, Naito T, Saito M. Current perspectives in human T-cell leukemia virus type 1 infection and its associated diseases. Front Med (Lausanne) 2022; 9: 867478.
4. Mozhgani S-H, Piran M, Zarei-Ghobadi M, Jafari M, Jazayeri S-M, Mokhtari-Azad T, et al. An insight to HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) pathogenesis; evidence from high-throughput data integration and meta-analysis. Retrovirology 2019; 16: 46.
5. Sato T, Yagishita N, Tamaki K, Inoue E, Hasegawa D, Nagasaka M, et al. Proposal of classification criteria for HTLV-1-associated myelopathy/tropical spastic paraparesis disease activity. Front Microbiol 2018; 9: 1651.
6. Martin F, Taylor GP, Jacobson S. Inflammatory manifestations of HTLV-1 and their therapeutic options. Expert Rev Clin Immunol 2014; 10: 1531-1546.
7. Hermine O, Ramos JC, Tobinai K. A review of new findings in adult T-cell leukemia–lymphoma: A focus on current and emerging treatment strategies. Adv Ther 2018; 35: 135-152.
8. Higuchi Y, Yasunaga J-i, Matsuoka M. HTLV-1's Foxy strategy for survival and transmission. Front Virol 2022; 1: 792659.
9. Kalinichenko S, Komkov D, Mazurov D. HIV-1 and HTLV-1 transmission modes: Mechanisms and importance for virus spread. Viruses 2022; 14: 152.
10. Sanchez-Vega F, Mina M, Armenia J, Chatila W, Luna A, La K, et al. Oncogenic signaling pathways in The Cancer Genome Atlas. Cell 2018; 173: 321-337. e10.
11. Hartmaier RJ, Albacker LA, Chmielecki J, Bailey M, He J, Goldberg ME, et al. High-throughput Genomic profiling of adult solid tumors reveals novel insights into cancer pathogenesis. Cancer Res 2017;77:2464-2475.
12. Schram AM, Berger MF, Hyman DM. Precision oncology: Charting a path forward to broader deployment of genomic profiling. PLoS Med 2017; 14(2): e1002242.
13. Sholl LM, Do K, Shivdasani P, Cerami E, Dubuc AM, Kuo FC, et al. Institutional implementation of clinical tumor profiling on an unselected cancer population. JCI Insight 2016; 1(19): e87062.
14. Zehir A, Benayed R, Shah RH, Syed A, Middha S, Kim HR, et al. Mutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients. Nat Med 2017; 23: 703-713.
15. Rovida E, Tusa I. Targeting MAPK in cancer 2.0. Int J Mol Sci 2022; 23: 5702.
16. Chilamakuri R, Agarwal S. Direct targeting of the raf-MEK-ERK signaling cascade inhibits Neuroblastoma growth. Curr Oncol 2022; 29: 6508-6522.
17. Wang W, Xu C, Wang D, Zhu Y, Zhuang W, Fang M, et al. P70. 05 The Association between MAP2K1 mutation class and clinical features in MAP2K1-mutant East Asian non-small cell lung cancer patients. J Thorac Oncol 2021; 16: S564.
18. Ghobadi MZ, Emamzadeh R, Mozhgani S-H. Deciphering microRNA-mRNA regulatory network in adult T-cell leukemia/lymphoma; the battle between oncogenes and anti-oncogenes. PLoS One 2021; 16(2): e0247713.
19. Pourrezaei S, Shadabi S, Gheidishahran M, Rahimiforoushani A, Akhbari M, Tavakoli M, et al. Molecular epidemiology and phylogenetic analysis of human T-lymphotropic virus type 1 in the tax gene and it association with adult t-cell leukemia/lymphoma disorders. Iran J Microbiol 2021; 13: 509-517.
20. Rafatpanah H, Torkamani M, Valizadeh N, Vakili R, Meshkani B, Khademi H, et al. Prevalence and phylogenetic analysis of HTLV‐1 in a segregated population in Iran. J Med Virol 2016; 88: 1247-1253.
21. Mozhgani S-H, Jahantigh HR, Rafatpanah H, Valizadeh N, Mohammadi A, Basharkhah S, et al. Interferon lambda family along with HTLV-1 proviral load, tax, and HBZ implicated in the pathogenesis of myelopathy/tropical spastic paraparesis. Neurodegener Dis 2018;18:150-5.
22. Aghamahdi F, Shafiee A, Rostami S, Mokhames Z, Safavi M, Yaslianifard S, et al. Comparative study of CNR1 and CNR2 cannabinoid receptors expression levels in COVID-19 patients with and without diabetes mellitus: Recommendations for future research targets. Diabetes Metab Syndr 2022; 16: 102499.
23. Ramezani S, Shirdel A, Rafatpanah H, Akbarin MM, Tarokhian H, Rahimi H, et al. Assessment of HTLV-1 proviral load, LAT, BIM, c-FOS and RAD51 gene expression in adult T cell leukemia/lymphoma. Med Microbiol Immunol 2017; 206: 327-335.
24. Meysami P, Alavian SM, Monavari SH, Mozhgani SH, Taghizadeh M, Farahani M, et al. Molecular characterization of hepatitis D virus genotypes circulating in Iran. Future Virol 2018;13: 265-273.
25. Soltani S, Mozhgani SH, Siri G, Emadi MS, Foroushani AR, Jazayeri SM, et al. High Expression of Inflammatory Cytokines and Chemokines in Human T-lymphotropic Virus 1-Associated Adult T-cell Leukemia/Lymphoma. Jundishapur J Microbiol 2022; 15(10): e132348.
26. Choi YL, Soda M, Ueno T, Hamada T, Haruta H, Yamato A, et al. Oncogenic MAP2K1 mutations in human epithelial tumors. Carcinogenesis 2012; 33: 956-961.
27. Estep AL, Palmer C, McCormick F, Rauen KA. Mutation analysis of BRAF, MEK1 and MEK2 in 15 ovarian cancer cell lines: implications for therapy. PLoS One 2007; 2(12): e1279.
28. Marks JL, Gong Y, Chitale D, Golas B, McLellan MD, Kasai Y, et al. Novel MEK1 mutation identified by mutational analysis of epidermal growth factor receptor signaling pathway genes in lung adenocarcinoma. Cancer Res 2008; 68: 5524-5528.
29. Bentivegna S, Zheng J, Namsaraev E, Carlton VE, Pavlicek A, Moorhead M, et al. Rapid identification of somatic mutations in colorectal and breast cancer tissues using mismatch repair detection (MRD). Hum Mutat 2008; 29: 441-450.
30. Williams EA, Montesion M, Shah N, Sharaf R, Pavlick DC, Sokol ES, et al. Melanoma with in-frame deletion of MAP2K1: A distinct molecular subtype of cutaneous melanoma mutually exclusive from BRAF, NRAS, and NF1 mutations. Mod Pathol 2020; 33: 2397-2406.
31. Mohammadpour M, Najd Mazhar F, Rajei M, Razi S, Rashidi H, Hassanzdeh M. Melorheostosis in proximal phalanx and metacarpal bone: a short-mid-term follow up. Mod Med Lab J 2022; 5: 56-60.
32. Brown NA, Furtado LV, Betz BL, Kiel MJ, Weigelin HC, Lim MS, et al. High prevalence of somatic MAP2K1 mutations in BRAF V600E–negative Langerhans cell histiocytosis. Blood 2014; 124: 1655-1658.
| Files | ||
| Issue | Vol 15 No 3 (2023) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijm.v15i3.12910 | |
| Keywords | ||
| Human T-lymphotropic virus type 1; HTLV-I-associated myelopathy; Tropical spastic paraparesis; Adult T-cell leukemia/lymphoma; Mitogen-activated protein kinase kinase 1; MAP kinase/ERK kinase | ||
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Hosseini P, Rahimi Foroushani A, Marjani A, Tavakoli M, Amiri A, Hosseini A, Bahavar A, Mozhgani S-H, Norouzi M. Investigating the effect of MAP2K1 gene (MEK1) in MAPK pathway in the induction of adult T-cell leukemia/lymphoma (ATLL). Iran J Microbiol. 2023;15(3):475-481.
