MicroRNA Analysis for Extramedullary Multiple Myeloma Relapse

Česká verzia

Authors: J. Gregorová ¹; D. Vrábel ¹; L. Radová ²; NA. Gablo ²; M. Almaši ³ ; M. Štork ⁴; O. Slabý ²; L. Pour ⁴; J. Minařík ⁵; S. Ševčíková ^1,3
Authors place of work: Babákova myelomová skupina, Ústav patologické fyziologie, LF MU, Brno ¹; CEITEC – Středoevropský technologický institut, MU, Brno ²; Oddělení klinické hematologie, FN Brno ³; Interní hematologická a onkologická klinika LF MU a FN Brno ⁴; Hemato-onkologická klinika LF UP a FN Olomouc ⁵
Published in the journal: Klin Onkol 2018; 31(Supplementum1): 148-150
Category: Článek ve sborníku

Summary

Introduction and Aims:
Multiple myeloma (MM) is the second most common hematooncological disease. Patient survival has been greatly improved by the introduction of new drugs into clinical practice, but survival is negatively affected by the so-called extramedullary relapse (EM), caused by the loss of plasma cell dependence on the bone marrow microenvironment and their migration out of the bone marrow. The nature and causes of this process are currently unclear. MicroRNAs (miRNAs) are short, non-coding RNA molecules involved in many physiological and pathological processes. Their significance in the pathogenesis of MM has been demonstrated by several studies. We assume that they are also involved in the development of the EM. The aim of this study was to analyze different miRNA expression between MM and EM patients.

Material and Methods:
Using next generation sequencing, we analyzed 39 samples of bone marrow cells from MM patients at diagnosis and 9 bone marrow plasma samples of EM patients.

Results:
In total, 2,278 miRNA were sequenced, but only 658 miRNAs were analyzed as they were expressed in all samples and had at least 20 reads. Expression data were generated using the Chimira tool from fastq data. All sequences were mapped using miRBase v20. Further analyses were performed using the R/Bioconductor package. The Bayesian procedure was used for normalization of expression. P values were adjusted using the Benjamini-Hochberg method. Analysis found 10 miRNA (p < 0.0005) that are statistically significantly expressed in EM vs. MM patients – these are miR-26a-5p, miR-26b-5p, miR-30e-5p, miR-424-3p, miR-503-5p, miR-767-5p, miR-105-5p, miR-5695-5p, miR-450b-5p and miR-92b-3p. These miRNAs will be further verified by qPCR method on a larger set of MM and EM patients.

Conclusion:
Our pilot study has shown that there are differentially expressed miRNAs between MM and EM patients.

Key words:
multiple myeloma – microRNA – carcinogenesis – next generation sequencing

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers

This work was supported by grant MZ ČR AZV 17- 29343A.

Submitted:
17. 3. 2018

Accepted:
20. 3. 2018

Zdroje

1. Calore F, Lovat F, Garofalo M. Non-coding RNAs and cancer. Int J Mol Sci 2013; 14 (8): 17085–17110. doi: 10.3390/ijms140817085.

2. Šána J, Faltejsková P, Svoboda M et al. Novel classes of non-coding RNAs and cancer. J Transl Med 2012; 10: 103. doi: 10.1186/1479-5876-10-103.

3. Ma L, Bajic VB, Zhang Z, 2013. On the classification of long non-coding RNAs. RNA Biol 2013; 10 (6): 924–933. doi: 10.4161/rna.24604.

4. Mattick JS. Non-coding RNAs: the architects of eukaryotic complexity. EMBO Rep 2001; 2 (11): 986–991. doi: 10.1093/embo-reports/kve230.

5. Guttman M, Amit I, Garber M et al. Chromatin signature reveals over a thousand highly conserved large non-coding RNAs in mammals. Nature 2009; 458 (7235): 223–227. doi: 10.1038/nature07672.

6. Ayers D. Long non-coding RNAs: novel emergent biomarkers for cancer diagnostics. J Cancer Res Treat 2013; 1 (2): 31–35.

7. Esteller M. Non-coding RNAs in human disease. Nature 2011; 12 (12): 861–874. doi: 10.1038/nrg3074.

8. Olsen PH, Ambros V. The lin-4 regulatory RNA controls developmental timing in caenorhabditis elegans by blocking LIN-14 protein synthesis after the initiation of translation. Dev Biol 1999; 216 (2): 671–680. doi: 10.1006/dbio.1999.9523.

9. Bagga S, Bracht J, Hunter S et al. Regulation by let-7 and lin-4 miRNAs results in target mRNA degradation. Cell 2005; 122 (4): 553–563. doi: 10.1016/j.cell.2005.07.031.

10. Lim LP, Lau NC, Garrett-Engele P et al. Microarray analysis shows that some microRNAs downregulate large numbers of target mRNAs. Nature 2005; 433 (7027): 769–773. doi: 10.1038/nature03315.

11. Esquela-Kerscher A, Slack FJ. Oncomirs – microRNAs with a role in cancer. Nat Rev Cancer 2006; 6 (4): 259–269. doi: 10.1038/nrc1840.

12. Hájek R, Krejci M, Pour L et al.2011. Multiple myeloma. Klin Onkol 2011; 24 (Suppl 1): 10–13. doi: 10.14735/amko20111S10.

13. Pour L, Sevcikova S, Greslikova H et al. Soft-tissue extramedullary multiple myeloma prognosis is significantly worse in comparison to bone-related extramedullary relapse. Haematologica 2014; 99 (2): 360–364. doi: 10.3324/haematol.2013.094409.

14. Usmani SZ, Heuck C, Mitchell A et al. Extramedullary disease portends poor prognosis in multiple myeloma and is overrepresented in high risk disease even in era of novel agents. Haematologica 2012; 97 (11): 1761–1767. doi: 10.3324/haematol.2012.065698.

15. Katodritou E, Gastari V, Verrou E et al. Extramedullary (EMP) relapse in unusual locations in multiple myeloma: Is there an association with precedent thalidomide administration and a correlation of special biological features with treatment and outcome? Leuk Res 2009; 33 (8): 1137–1140. doi: 10.1016/j.leukres.2009.01.036.

16. Short KD, Rajkumar SV, Larson D et al. Incidence of extramedullary disease in patients with multiple myeloma in the era of novel therapy, and the activity of pomalidomide on extramedullary myeloma. Leukemia 2011; 25 (6): 906–908. doi: 10.1038/leu.2011.29.

17. Varga C, Xie W, Laubach J et al. Development of extramedullary myeloma in the era of novel agents: no evidence of increased risk with lenalidomide-bortezomib combinations. Br J Haematol 2015; 169 (6): 843–850. doi: 10.1111/bjh.13382.

18. Churg J, Gordon AJ. Multiple myeloma with unusual visceral involvement. Arch Pathol 1942; 34: 546–556.

19. Hayes DW, Bennett WA, Heck FJ. Extramedullary lesions in multiple myeloma: Review of literature and pathologic studies. AMA Arch Pathol 1952; 53 (3): 262–272.

20. Varettoni M, Corso A, Pica G et al. Incidence, presenting features and outcome of extramedullary disease in multiple myeloma: A longitudinal study on 1,003 consecutive patients. Ann Oncol 2010; 21 (2): 325–330. doi: 10.1093/annonc/mdp329.