Journal of Isfahan Medical School

Journal of Isfahan Medical School

The Relationship between the Gene Expression Level of MYC Gene and Non-Coding RNA Lnc-Myc-2-34 Dup1 in Acute Lymphoblastic Leukemia

Document Type : Original Article (s)

Authors
Kamal Shahamiri 1
Arash Alghasi 2
Najmaldin Saki 2
Gholam Abbas Kaydani 3
Hossein Teimori 1
1 Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran
2 Thalassemia and Hemoglobinopathy Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
3 Department of Laboratory Sciences, School of Allied Medical Sciences, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
10.48305/jims.v40.i675.0412
Abstract
Background: In recent years, an increasing trend in the incidence of acute lymphoblastic leukemia (ALL) has been reported. However, the molecular mechanisms involved are not fully understood. Because of the importance of c-MYC in ALL pathogenesis, it is important to consider the associated lncRNAs in identifying the molecular mechanisms involved in disease progression. The consequences of notch signals, depending on the dose and content can be highly pleiotropic. In hemolymphoid, notch signaling affects various cell lines at different stages of growth. The present study aimed to investigate the role of the MYC gene and related LncRNAs as a potential target for the treatment of acute lymphoblastic leukemia.
Methods: This case-control study was performed on 40 ALL patients and 40 healthy controls during the years 2020-2021. For this purpose, total RNA was extracted from blood samples and after cDNA synthesis, MYC,
and-myc-2-34 dup1 expression was measured using Real-Time PCR. Statistical analysis of the results was performed using SPSS software and appropriate tests.
Findings: The results of the gene expression study showed that in patients with ALL, MYC expression and related lncRNA lnc-myc-2-34 dup1 compared to controls had significant increases. These expression changes were not significantly different in age, sex, MRD, and T-ALL and B-ALL categories. lncRNA lnc-myc-2-34 dup1 correlated with the MYC gene, and the ROC curve indicated their potential as a strong biomarker.
Conclusion: Using lncRNAs as diagnostic, prognostic, and therapeutic markers can be an appropriate option that needs further research. According to the present study findings, the increased expression of myc-2-34 dup1 in patients with ALL has been reported for the first time thus, can be used as strong biomarkers.
Keywords
Acute lymphoblastic leukemia
MYC oncogene
Long Noncoding RNA
Case-control studies
Gene expression
  1. Hunger SP, Mullighan CG. Acute lymphoblastic leukemia in children. N Engl J Med 2015; 373(16): 1541-52.
  2. Terwilliger T, Abdul-Hay M. Acute lymphoblastic leukemia: a comprehensive review and 2017 update. Blood Cancer J 2017; 7: e577.
  3. Rehman A, Abbas N, Saba T, Ur Rahman SI, Mehmood Z, Kolivand H. Classification of acute lymphoblastic leukemia using deep learning. Microscopy Research and Technique, 2018. 81(11): p. 1310-17.
  4. Iacobucci I, Mullighan CG. Genetic basis of acute lymphoblastic leukemia. J Clin Oncol 2017; 35(9): 975-83.
  5. Arman K, Möröy T. Crosstalk between MYC and lncRNAs in hematological malignancies. Front Oncol. 2020; 10: 579940.
  6. Bustos Fernández L. Colon: Structure and function. Berlin, Germany: Springer Science & Business Media; 2013.
  7. Kato M, Manabe A. Treatment and biology of pediatric acute lymphoblastic leukemia. Pediatr Int 2018; 60(1): 4-12.
  8. Fang Y, Fullwood MJ. Roles, functions, and mechanisms of long non-coding RNAs in cancer. Genomics Proteomics Bioinformatics 2016; 14(1): 42-54.
  9. Arun G, Diermeier SD, Spector DL. Therapeutic targeting of long non-coding RNAs in cancer. Trends Mol Med 2018; 24(3): 257-77.
  10. Liang J, Chen W, Lin J. LncRNA: an all-rounder in rheumatoid arthritis. J Transl Int Med 2019; 7(1): 3-9.
  11. Li G, Gao L, Zhao J, Liu D, Li H, Hu M. LncRNA ANRIL/miR-7-5p/TCF4 axis contributes to the progression of T cell acute lymphoblastic leukemia. Cancer Cell Int 2020; 20: 335.
  12. Li S, Bian H, Cao Y, Juan C, Cao Q, Zhou G, et al. Identification of novel lncRNAs involved in childhood acute lymphoblastic leukemia pathogenesis. Oncology letters meant results 2019; 17(2): 2081-90.
  13. de Souza Melo CP, Campos CB, de Oliveira Rodrigues J, Aguirre-Neto JC, Atalla A, Pianovski MAD, et al. Long non-coding RNAs: biomarkers for acute leukemia subtypes. Br J Hematol 2016; 173(2): 318-20.
  14. Sheikh‐Zeineddini N, Safaroghli-Azar A, Salari S, Bashash D. C-Myc inhibition sensitizes pre-B ALL cells to the anti-tumor effect of vincristine by altering apoptosis and autophagy: Proposing a probable mechanism of action for 10058-F4. Eur J Pharmacol 2020; 870: 172821.
  15. Weng AP, Millholland JM, Yashiro-Ohtani Y, Arcangeli ML, Lau A, Wai C, et al. c-Myc is an important direct target of Notch1 in T-cell acute lymphoblastic leukemia/lymphoma. Genes Dev 2006. 20(15): 2096-109.
  16. Allen A, Gill K, Hoehn D, Sulis M, Bhagat G, Alobeid B. C-myc protein expression in B-cell acute lymphoblastic leukemia, prognostic significance? Leuk Res 2014; 38(9): 1061-6.
  17. Ott CJ, Kopp N, Bird L, Paranal RM, Qi J, Bowman T, et al. BET bromodomain inhibition targets both c-Myc and IL7R in high-risk acute lymphoblastic leukemia. Blood 2012; 120(14): 2843-52.
  18. Wallington-Beddoe CT, Powell JA, Tong D, Pitson SM, Bradstock KF, Bendall LJ. Sphingosine kinase 2 promotes acute lymphoblastic leukemia by enhancing MYC expression. Cancer Res 2014; 74(10): 2803-15.
  19. Bressanin D, Evangelisti C, Ricci F, Tabellini G, Chiarini F, Tazzari PL, et al. Harnessing the PI3K/Akt/mTOR pathway in T-cell acute lymphoblastic leukemia: eliminating activity by targeting at different levels. Oncotarget 2012; 3(8): 811-23.
  20. Bertacchini J, Heidari N, Mediani L, Capitani S, Shahjahani M, Ahmadzadeh A, et al. Targeting PI3K/AKT/mTOR network for the treatment of leukemia. Cell Mol Life Sci 2015; 72(12): 2337-47.
  21. Safaroghli-Azar A, Sadri M, Bashash D. Bashash, Induction of p21-and p27-mediated cell cycle arrest in Nalm-6 cells using pan-PI3K inhibitor (Buparlisib)
    [in Persian]. KoMesh 2018; 20(4): 756-63.
  22. Fernando TR, Rodriguez-Malave NI, Waters EV, Yan W, Casero D, Basso G, et al. LncRNA expression discriminates karyotype and predicts survival in B-lymphoblastic leukemia. Mol Cancer Res 2015; 13(5): 839-51.
  23. Yeoh EJ, Ross ME, Shurtleff SA, Williams WK, Patel D, Mahfouz R, et al. Classification, subtype discovery, and prediction of outcome in pediatric acute lymphoblastic leukemia by gene expression
    Cancer cell 2002; 1(2): 133-43.
  24. Ouimet M, Drouin S, Lajoie M, Caron M, St-Onge P, Gioia R, et al. A childhood acute lymphoblastic leukemia-specific lncRNA implicated in prednisolone resistance, cell proliferation, and migration. Oncotarget 2017; 8(5): 7477-88.
  25. Wang Y, Wu P, Lin R, Rong L, Xue Y, Fang Y. LncRNA NALT interaction with NOTCH1 promoted cell proliferation in pediatric T cell acute lymphoblastic leukemia. Sci Rep 2015; 5: 13749.
Journal of Isfahan Medical School
Volume 40, Issue 675
3rd Week, August
Summer 2022
Pages 412-420

  • Receive Date 14 August 2022