General AML

Serum miR-223 expression in patients with acute myeloid leukemia

MicroRNAs (miRNAs) are single stranded, small, non-coding RNAs which are known to play an important role in many biological processes and are detectable in serum and plasma samples. Aberrant expression of several miRNAs (miR-155, miR-210, miR-126-5p, miR-370, miR-328, and miR-204) have been associated with outcome in acute myeloid leukemia (AML).1-6 Recently, low serum expression of miR-223 has been implicated in the development of AML.7-9

Guopan Yu, Nanfang Hospital, Guangzhou, CN, and team compared serum levels of miR-223 in 131 patients with AML and 70 healthy controls who had no cancer symptoms or clinical signs of any other disease.10 RNA was extracted from serum and reverse transcribed prior to quantitative real time polymerase chain reaction (qPCR) being performed for both miR-223 and for a control miRNA that had been spiked into the sample at a known concentration during RNA purification.

Key findings
  • There was a significant reduction in expression of miR-223 in the AML group compared with the control group (p< 0.05)
  • Receiver operating characteristic curve analysis demonstrated that miR-223 levels could differentiate AML from the controls with a sensitivity of 83.2% and a specificity of 81.4%
  • Serum miR-223 levels were higher in the favorable than in the intermediate/unfavorable cytogenetic risk groups and in patients in who achieved complete remission (CR), whereas low miR-223 was more often associated with higher risk cytogenetics and blasts in bone marrow (Table 1)
  • miR-223 expression levels pre- and post-induction chemotherapy were compared and the levels of miR-223 post-induction were higher than they had been at pre-induction in both the patients who had achieved CR (p< 0.01) and those who had not (p< 0.05)
  • Overall survival (OS) and relapse-free survival at 5 years were significantly shorter for those patients who had lower miR-223 expression levels (p= 0.021 and p= 0.003, respectively)
  • Univariate and multivariate analysis showed that miR-223 is an independent predictor of OS in patients with AML (risk ratio [RR] 3.54; 95% confidence interval [CI], 1.47–5.79; p= 0.016 and RR 4.25; 95% CI, 1.29–7.38; p= 0.011, respectively)
  • There was no association between miR-223 expression and age, gender, white blood cells, or platelets

Table 1: Serum miR-223 expression in AML cases

 

Patients

(n= 131)

Low miR-223

(n= 69)

High miR-223

(n= 62)

p value

Cytogenetics

Favorable

Intermediate

Unfavorable

 

52

61

18

 

16

38

15

 

36

23

3

 

< 0.0001

Complete remission

Yes

No

 

55

76

 

20

49

 

35

27

 

0.0015

Blasts in bone marrow

< 50%

≥ 50%

 

54

77

 

21

48

 

33

29

 

 0.0081

Guopan Yu and colleagues state that their work is in agreement with previous work on miR-223 in AML.7-9 miR-223 regulates the equilibrium between expansion and differentiation in hematopoietic stem and progenitor cells, and expression of miR-223 leads to the production of red blood cells, T cells and B cells. Expression of miR-223 inhibits cell proliferation and increases apoptosis in AML cell lines, and knocking down miR-223 increases the frequency of myeloid progenitors. The authors discussed how decreased expression of miR-223 seems to be associated with nasopharyngeal carcinoma, cervical cancer, gallbladder cancer, hepatocellular carcinoma, and breast cancer, yet increased expression is seen in gastric cancer, colon cancer, and non-small cell lung cancer.10  The group conclude that miR-223 may be able to be used as diagnostic tool and as a predictor of poor patient outcome in patients with AML.

References
  1. Xu L.H. et al. Overexpressed miR‐155 is associated with initial presentation and poor outcome in Chinese pediatric acute myeloid leukemia. Eur Rev Med Pharmaco. 2015 Dec; 19(24):4841–4850
  2. Tang X. et al. Overexpression of miR‐210 is associated with poor prognosis of acute myeloid leukemia. Med Sci Monitor. 2015 Nov 09; 21:3427–3433. DOI: 10.12659/MSM.894812
  3. Shibayama Y. et al. Upregulation of microRNA‐126‐5p is associated with drug resistance to cytarabine and poor prognosis in AML patients. Oncol Rep. 2015 May; 33(5):2176–2182. DOI: 10.3892/or.2015.3839
  4. Lin X. et al. Serum MicroRNA‐370 as a potential diagnostic and prognostic biomarker for pediatric acute myeloid leukemia. Int J Clin Exp Pathol. 2015 Nov; 8(11):14658–14666
  5. Liu L. et al. Low expression of circulating microRNA‐328 is associated with poor prognosis in patients with acute myeloid leukemia. Diagn Pathol. 2015 Jul 17; 10:109. DOI: 10.1186/s13000-015-0345-6
  6. Butrym A. et al. Low expression of microRNA‐204 (miR‐204) is associated with poor clinical outcome of acute myeloid leukemia (AML) patients. J Exp Clin Canc Res. 2015 Jul 01; 34:68. DOI: 10.1186/s13046-015-0184-z
  7. Xiao Y. et al. MiR‐223 decreases cell proliferation and enhances cell apoptosis in acute myeloid leukemia via targeting FBXW7. Oncol Lett. 2016 Nov; 12(5):3531–3536. DOI: 10.3892/ol.2016.5115
  8. Pulikkan J.A. et al. Cell‐cycle regulator E2F1 and microRNA‐223 comprise an autoregulatory negative feedback loop in acute myeloid leukemia. Blood. 2010 Mar 04; 115(9):1768–1778. DOI: 10.1182/blood-2009-08-240101
  9. Gentner B. et al. MicroRNA‐223 dose levels fine tune proliferation and differentiation in human cord blood progenitors and acute myeloid leukemia. Exp Hematol. 2015 Oct; 43(10):858–868.e7. DOI: 10.1016/j.exphem.2015.05.018
  10. Yu G. et al. Low serum miR‐223 expression predicts poor outcome in patients with acute myeloid leukemia. J Clin Lab Anal. 2019 Nov 6:e23096. DOI: 10.1002/jcla.23096. [Epub ahead of print]
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