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. 2018 Apr 10;9(27):19136-19146.
doi: 10.18632/oncotarget.24927.

Assessment of micro RNAs expression in leukemic cells as prognostic markers in chronic lymphocytic leukemia: micro RNAs can predict survival in a course of the disease

Agnieszka Szymczyk  1   2 , Sylwia Chocholska  1 , Arkadiusz Macheta  1 , Dariusz Szczepanek  3 , Marek Hus  1 , Monika Podhorecka  1
Affiliations

Assessment of micro RNAs expression in leukemic cells as prognostic markers in chronic lymphocytic leukemia: micro RNAs can predict survival in a course of the disease

Agnieszka Szymczyk et al. Oncotarget. .

Abstract

Numerous genetic alterations predicting prognosis and clinical outcome are revealed recently in chronic lymphocytic leukemia (CLL). Among them the deregulated expression of micro RNAs that can induce tumor growth, or act as tumor suppressors seem to be of great importance. This study aimed to analyze the possible role of chosen micro RNAs as markers of prognosis in patients with CLL. We assessed the expression of miR-21, miR-34a, miR-181a, miR-199a/b and miR-221 in previously separated leukemic cells with the use of qRQ-PCR technique at the moment of diagnosis. The results were then analyzed in regards to presence of prognostic factors, clinical data and the end points like progression free survival (PFS), time to progression (TP) and overall survival time (OS). We detected significant correlations between expression of the analyzed micro RNAs and CLL prognostic markers particularly as far as miR-221 and miR-181a were concerned. The subsequent analysis revealed that high expression of miR-34a and miR-181a as well as low miR-21 expression indicated longer TTP, while miR-221 was predictor of OS. The obtained results prove the role of micro RNAs as CLL prognostic markers, particularly as factors predicting survival in a course of the disease.

Keywords: chronic lymphocytic leukemia; micro RNA; overall survival; prognostic factors; progression free survival.

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Conflict of interest statement

CONFLICTS OF INTEREST There were no conflicts of interest.

Figures

Figure 1
Figure 1. Correlations between micro RNAs expression and prognostic factors of CLL
(A) Correlation between miR-221 expression and both leucocytosis and lymphocytosis. (B) Correlation between miR-181a expression and of β2-mikroglobulin level and between miR-221 expression and β2-mikroglobulin level. (C) Correlation between miR-181a expression and CD38 expression and between miR-221 expression and CD38 expression. (D) Micro RNAs expression in high risk cytogenetic patients versus standard risk group.
Figure 2
Figure 2. Expression of miR-34a in relation to time to progression (TTP)
(A) miR-34a level in patients with moment of progression which occurred within 1 year after diagnosis (n = 14) and in subjects with time to progression longer than 1 year (n = 6). (B) Kaplan–Meier analysis of progression probability in a group of patients with high versus low expression of miR-34a.
Figure 3
Figure 3. Multivariate linear regression analysis assessing influence of all studied micro RNAs on time to progression (TTP)
(A) Expression of miR-21 versus TTP. (B) Expression of miR-34a versus TTP. (C) Expression of miR-181a versus TTP. (D) Data of numerical analysis.
Figure 4
Figure 4. Expression of miR-221 in relation to overall survival (OS)
(A) miR-221 level in patients who survived less than 5 years (n = 16) and those who survived more than 5 years (n = 24). (B) Kaplan–Meier analysis of progression probability in a group of patients with high versus low expression of miR-221.
See this image and copyright information in PMC

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