PB1889 PROGNOSTIC VALUE OF MICRORNA‐223 IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA
Authors: Berezina O.V. , Basharova R.R. , Perepechaeva M.L. , Agakishiev M.M. , Kovinev I.B. , Nechunaeva I.N. , Grishanova A.Y. , Pospelova T.I. 
Published: June 2019

Background:

Various microRNAs (miR), including miR‐223, are involved in the pathogenesis of chronic lymphocytic leukemia (CLL) and can be considered as potential molecular markers of the disease.

Aims:

To determine the prognostic role of miR‐223 in the patients with chronic lymphocytic leukemia

Methods:

The study population consisted of 35 patients with CLL. The age of the patients was 63.37 ± 8.67 years (mean ± SD); 23 of them were men (66%), and 12 women (34%). Ten patients had stage A of the disease (29%), 19 patients stage B (54%), and six patients stage C (17%). Based on a molecular genetic tes, 11 patients (31%) were classified as an unfavorable prognosis group, 24 patients (69%) were included in the second group without adverse genetic aberrations. Indications for treatment were found in 21 patients (60%). Of these, 13 patients (62%) achieved an optimal response (partial or complete remission) to standard polychemotherapy, and eight patients (38%) experienced progression of the disease.

Total RNA was isolated from the venous blood (plasma, lymphocytes, and extracellular vesicles) and bone marrow of the patients using the TRIzol RNA extraction kit (Ambion, USA). MiRNA expression was evaluated by real‐time PCR according to the TaqMan principle. To evaluate the miR‐223 expression, the ΔCT method was chosen. As a gene for normalization, small nuclear U6 RNA was selected.

Statistical significance of differences between the mean values was determined by Student's t test and U test (Mann–Whitney test). The results were considered statistically significant at p < 0.05.

Results:

In the unfavorable‐prognosis group, expression of miR‐223 in plasma was 1.4 ± 0.62, in lymphocytes 1.5 ± 0.57, in extracellular vesicles 9.65 ± 8.67, and in bone marrow 4.89 ± 3.15, whereas in the second group, these figures were 0.47 ± 0.31, 3.51 ± 1.69, 2.31 ± 1.47, and 4.11 ± 2.83, respectively. The differences were statistically insignificant. In the group of patients with advanced stages of the disease (B and C), which also indicate progression of the disease, a decrease in the expression of miR‐223 was observed as compared with the initial stage (A): in plasma, 0.4 ± 0.29 versus 302.19 ± 172.83 (p ≤ 0.002); in lymphocytes, 1.13 ± 0.68 versus 10.21 ± 3.35 (p ≤ 0.04); and in bone marrow, 2.95 ± 0.94 versus 4.17 ± 1.77 (p ≤ 0, 01). MiR‐223 has not been shown previously to change expression with the progression of CLL, and in some cases, its decline has been documented, as is the case for such B‐cell cancers as lymphoma of the mantle zone and lymphoma of the marginal zone, which is associated with epigenetic “silencing” of some genes.

The response to treatment is one of the indicators of long‐term prognosis of a disease. During comparison of the two groups, it was noted that patients who did not achieve the optimal response to treatment had a low level of miR‐223 before initiation of treatment as compared to patients who attained partial or complete remission: in plasma, 0.67 ± 0.15 vs. 0.94 ± 0.89 (p ≤ 0.04), in extracellular vesicles 2.3 ± 1.03 vs. 12.11 ± 3.46 (p ≤ 0.001), and in bone marrow 15.06 ± 4.21 vs. 65.16 ± 17.36 (p ≤ 0.01). These data are consistent with the results of some studies showing that a decrease in the level of miR‐223 is a marker of unfavorable prognosis and resistance to treatment.

Summary/Conclusion:

MiR‐223 was present in all the analyzed blood components and bone marrow in patients with CLL. Low expression of miR‐223 is associated with an unfavorable prognosis of the disease, which makes it possible to consider this miRNA as an additional prognostic marker in CLL.