Association between microRNA-21, microRNA-150, and microRNA-451 expression and clinical outcome of patients with acute lymphoblastic leukemia
Received date: 29 Oct 2016
Accepted date: 30 Dec 2016
Published date: 28 Feb 2017
Copyright
BACKGROUND: Acute lymphoblastic leukemia (ALL) occurs owing to the defective maturation, increased proliferation, and lack of differentiation of lymphoid cells. Evaluation of the expression levels of microRNAs (miRNAs) could help in the prognosis and improve the clinical outcome of ALL patients. Given the role of miR-21, miR-150, and miR-451 as oncogenes and tumor suppressors in lymphocytes, this study explored the relation between the expression levels of these miRNAs and the clinical outcomes of ALL patients.
METHODS: cDNA synthesis and RT-PCR were performed for peripheral blood samples from 41 patients with ALL, as well as for U937 and Jurkat cell lines to examine the expression of miR-451, miR-150, and miR-21 after miRNA purification. We also performed an epidemiological analysis in which Mann–Whitney and Chi-square tests were used to investigate the relationship between the expression of miRNAs and other clinical and laboratory data. Binary logistic regression models were used to estimate the odds ratio in univariate and multivariate analyses for clinical outcomes.
RESULTS: miR-21 and miR-150 expression was found to be decreased, while miR-451 expression showed no difference compared to the control group. There was a significant relationship between miR-451 expression and hemoglobin (Hb) levels, as well as between miR-150 expression and clinical outcomes of ALL patients.
CONCLUSION: Increased expression of miR-451 decreased the Hb levels; reduced expression of miR-150 was associated with increased relapse rate in patients. Age, increased WBC, and decreased Hb levels were associated with increased relapse rates in ALL patients. Therefore, miR-150 could be used as a biomarker to determine the clinical outcome of ALL patients.
Key words: acute lymphoblastic leukemia; miRNA; clinical outcome
Ali Amin Asnafi , Elahe Khodadi , Neda Golchin , Arash Alghasi , Yousef Tavakolifar , Najmaldin Saki . Association between microRNA-21, microRNA-150, and microRNA-451 expression and clinical outcome of patients with acute lymphoblastic leukemia[J]. Frontiers in Biology, 2017 , 12(1) : 63 -70 . DOI: 10.1007/s11515-016-1437-8
1 |
Anindo M I K, Yaqinuddin A (2012). Insights into the potential use of microRNAs as biomarker in cancer. Int J Surg, 10(9): 443–449
|
2 |
Babashah S, Sadeghizadeh M, Tavirani M R, Farivar S, Soleimani M (2012). Aberrant microRNA expression and its implications in the pathogenesis of leukemias. Cell Oncol (Dordr), 35(5): 317–334
|
3 |
Bai H, Xu R, Cao Z, Wei D, Wang C (2011). Involvement of miR-21 in resistance to daunorubicin by regulating PTEN expression in the leukaemia K562 cell line. FEBS Lett, 585(2): 402–408
|
4 |
Bustin S A, Benes V, Garson J A, Hellemans J, Huggett J, Kubista M, Mueller R, Nolan T, Pfaffl M W, Shipley G L, Vandesompele J, Wittwer C T (2009). The MIQE guidelines: minimum information for publication of quantitative real-time PCR experiments. Clin Chem, 55(4): 611–622
|
5 |
Duyu M, Durmaz B, Gunduz C, Vergin C, Yilmaz Karapinar D, Aksoylar S, Kavakli K, Cetingul N, Irken G, Yaman Y, Ozkinay F, Cogulu O (2014). Prospective evaluation of whole genome microRNA expression profiling in childhood acute lymphoblastic leukemia. BioMed Res Int, 2014: 967585
|
6 |
Ghisi M, Corradin A, Basso K, Frasson C, Serafin V, Mukherjee S, Mussolin L, Ruggero K, Bonanno L, Guffanti A, De Bellis G, Gerosa G, Stellin G, D’Agostino D M, Basso G, Bronte V, Indraccolo S, Amadori A, Zanovello P (2011). Modulation of microRNA expression in human T-cell development: targeting of NOTCH3 by miR-150. Blood, 117(26): 7053–7062
|
7 |
Gordon J E, Wong J J L, Rasko J E (2013). MicroRNAs in myeloid malignancies. Br J Haematol, 162(2): 162–176
|
8 |
Hussein K, Theophile K, Büsche G, Schlegelberger B, Göhring G, Kreipe H, Bock O (2010). Significant inverse correlation of microRNA-150/MYB and microRNA-222/p27 in myelodysplastic syndrome. Leuk Res, 34(3): 328–334
|
9 |
Lawrie C H (2013). MicroRNAs in hematological malignancies. Blood Rev, 27(3): 143–154
|
10 |
Li X, Sanda T, Look A T, Novina C D, von Boehmer H (2011). Repression of tumor suppressor miR-451 is essential for NOTCH1-induced oncogenesis in T-ALL. J Exp Med, 208(4): 663–675
|
11 |
Lopotová T, Záčková M, Klamová H, Moravcová J (2011). MicroRNA-451 in chronic myeloid leukemia: miR-451-BCR-ABL regulatory loop? Leuk Res, 35(7): 974–977
|
12 |
Naderi M, Abdul Tehrani H, Soleimani M, Shabani I, Hashemi S M (2015). A home-brew real-time PCR assay for reliable detection and quantification of mature miR-122. Appl Immunohistochem Mol Morphol, 23(8): 601–606
|
13 |
Pfaffl M W, Horgan G W, Dempfle L (2002). Relative expression software tool (REST) for group-wise comparison and statistical analysis of relative expression results in real-time PCR. Nucleic Acids Res, 30(9): e36–e36
|
14 |
Rossi S, Shimizu M, Barbarotto E, Nicoloso M S, Dimitri F, Sampath D, Fabbri M, Lerner S, Barron L L, Rassenti L Z, Jiang L, Xiao L, Hu J, Secchiero P, Zauli G, Volinia S, Negrini M, Wierda W, Kipps T J, Plunkett W, Coombes K R, Abruzzo L V, Keating M J, Calin G A (2010). microRNA fingerprinting of CLL patients with chromosome 17p deletion identify a miR-21 score that stratifies early survival. Blood, 116(6): 945–952
|
15 |
Saki N, Abroun S, Soleimani M, Hajizamani S, Shahjahani M, Kast R E, Mortazavi Y (2015). Involvement of MicroRNA in T-Cell Differentiation and Malignancy. Int J Hematol Oncol Stem Cell Res, 9(1): 33–49
|
16 |
Saki N, Abroun S, Soleimani M, Mortazavi Y, Kaviani S, Arefian E (2014). The roles of miR-146a in the differentiation of Jurkat T-lymphoblasts. Hematology, 19(3): 141–147
|
17 |
Salzman D W, Weidhaas J B (2013). SNPing cancer in the bud: microRNA and microRNA-target site polymorphisms as diagnostic and prognostic biomarkers in cancer. Pharmacol Ther, 137(1): 55–63
|
18 |
Shahrabi S, Azizidoost S, Shahjahani M, Rahim F, Ahmadzadeh A, Saki N (2014). New insights in cellular and molecular aspects of BM niche in chronic myelogenous leukemia. Tumour Biol, 35(11): 10627–10633
|
19 |
Shi C, Zhang X, Li X, Zhang L, Li L, Sun Z, Fu X, Wu J, Chang Y, Li W, Chen Q, Zhang M (2016). Effects of microRNA-21 on the biological functions of T-cell acute lymphoblastic lymphoma/leukemia. Oncol Lett, 12(5): 4173–4180
|
20 |
Tavakoli F, Jaseb K, Far M A J, Soleimani M, Khodadi E, Saki N (2016). Evaluation of microRNA-146a expression in acute lymphoblastic leukemia. Frontiers in Biology, 11(1): 53–58
|
21 |
Wang M, Tan L P, Dijkstra M K, van Lom K, Robertus J L, Harms G, Blokzijl T, Kooistra K, van T’veer M B, Rosati S, Visser L, Jongen-Lavrencic M, Kluin P M, van den Berg A (2008). miRNA analysis in B-cell chronic lymphocytic leukaemia: proliferation centres characterized by low miR-150 and high BIC/miR-155 expression. J Pathol, 215(1): 13–20
|
22 |
Whitman S P, Maharry K, Radmacher M D, Becker H, Mrózek K, Margeson D, Holland K B, Wu Y Z, Schwind S, Metzeler K H, Wen J, Baer M R, Powell B L, Carter T H, Kolitz J E, Wetzler M, Moore J O, Stone R M, Carroll A J, Larson R A, Caligiuri M A, Marcucci G, Bloomfield C D (2010). FLT3 internal tandem duplication associates with adverse outcome and gene- and microRNA-expression signatures in patients 60 years of age or older with primary cytogenetically normal acute myeloid leukemia: a Cancer and Leukemia Group B study. Blood, 116(18): 3622–3626
|
23 |
Yan L X, Huang X F, Shao Q, Huang M Y, Deng L, Wu Q L, Zeng Y X, Shao J Y (2008). MicroRNA miR-21 overexpression in human breast cancer is associated with advanced clinical stage, lymph node metastasis and patient poor prognosis. RNA, 14(11): 2348–2360
|
24 |
Zhao H, Wang D, Du W, Gu D, Yang R (2010). MicroRNA and leukemia: tiny molecule, great function. Crit Rev Oncol Hematol, 74(3): 149–155
|
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