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.