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Investigation of miR-21, miR-150, miR-155 Expression Levels in Chronic Myeloid Leukemia Patients

Year 2025, Volume: 9 Issue: 1, 74 - 81, 21.04.2025
https://doi.org/10.46332/aemj.1327364

Abstract

Purpose: In this study, the relationship between CML and the expression levels of miR-21, miR-150, and miR-155, which could be used in the follow-up of CML patients, was investigated.

Materials and Methods: RNA and miRNA were extracted from peripheral blood samples of patient and control samples. Targe-ted miRNA expression levels from cDNA samples were analyzed by real-time PCR method.

Results: miRNA expression level was determined as 1.0 in the control group. In the newly diagnosed group, the mean miR-21 fold change was 0.6, miR-150 fold change was 0.3, and miR-155 fold change was 0.5. fold changes for miR-21, miR-150 and miR-155 were found to be 1.4, 0.5 and 2.4 fold, respectively, in the imatinib treatment group. In the nilotinib treatment group, miR-21 level was 3.5, miR-150 level 0.5, and miR-155 level 4.3. In the dasatinib treatment group, fold change was 0.8 for miR-21, 2.1 for miR-150, and 0.5 for miR-155. The mean miR-21 level was found to be 3.2, miR-150 level 1.0 and miR-155 level 2.8. MiR-150 levels were found to be lower in the newly diagnosed group, imatinib group and nilotinib group than in the control samples. This difference between the new diagnosis group (p=0.07484) and the nilotinib group (p=0.01541) is statistically signi-ficant. No significant difference was found between patients and controls in terms of miR-21 and miR-155 levels.

Conclusion: These results support that miRNA-150 can be used as a parameter in the monitoring of treatment of CML patients and can contribute to the early detection of drug resistance.

Project Number

TYL 2018-8012

References

  • 1. Karaman A, Medeni ŞS, Sevindik ÖG ve ark. Kronik myeloid lösemi tanılı hastalarımızın retrospektif değerlendirilmesi. DEU Tıp Fak. Der. 2016;30(3):103-112.
  • 2. Goldman JM, Melo JV. Chronic myeloid leukemia advances in biology and new approaches to treatment. N Engl J Med. 2003;349(15):1451-1464.
  • 3. Sağ ŞÖ. Kronik Miyelositer Lösemilerde Füzyon Gen Kalitatif ve Kantitatif Değerlerinin FISH ve Moleküler Genetik Yöntemlerle Karşılaştırılması. Tıpta Uzmanlık Tezi, Bursa Uludag Üniversitesi; 2010.
  • 4. Di Bacco A, Keeshan K, McKenna SL, Cotter TG. Molecular abnormalities in chronic myeloid leukemia: deregulation of cell growth and apoptosis. Oncologist. 2000;5(5):405-415.
  • 5. Ali MA. Chronic Myeloid Leukemia in the Era of Tyrosine Kinase Inhibitors: An Evolving Paradigm of Molecularly Targeted Therapy. Mol Diagn Ther. 2016;20(4):315-333.
  • 6. Sun J, Hu R, Han M, et al. Mechanisms underlying therapeutic resistance of tyrosine kinase inhibitors in chronic myeloid leukemia. Int J Biol Sci. 2024;20(1): 175-181.
  • 7. Younes S, Ismail MA, Al-Jurf R, Ziyada A ve ark. Management of chronic myeloid leukaemia: current treatment options, challenges, and future strategies. Hematology. 2023;28(1):2196866.
  • 8. Krol J, Loedige I, Filipowicz W. The widespread regulation of microRNA biogenesis, function and decay. Nat Rev Genet. 2010;11(9):597-610.
  • 9. Almeida MI, Reis RM, Calin GA. MicroRNA history: discovery, recent applications, and next frontiers. Mutat Res. 2011;717(1-2):1-8.
  • 10. Wahid F, Shehzad A, Khan T, Kim YY. MicroRNAs: synthesis, mechanism, function, and recent clinical trials. Biochim Biophys Acta. 2010;1803(11):1231-1243.
  • 11. Reid G, Kirschner MB, Van Zandwijk N. Circulating microRNAs: Association with disease and potential use as biomarkers. Crit Rev Oncol Hematol. 2011;80(2):193-208.
  • 12. Etheridge A, Lee I, Hood L, ve ark. Extracellular microRNA: a new source of biomarkers. Mutat Res. 2011;717(1-2):85-90.
  • 13. Lujambio A and Lowe SW. The microcosmos of cancer. Nature. 2012;482(7385):347-355.
  • 14. Calin GA, Croce CM. MicroRNA signatures in human cancers. Nat Rev Cancer. 2006;6(11):857-866.
  • 15. Cho WC. OncomiRs: the discovery and progress of microRNAs in cancers. Mol Cancer. 2007;60(6):1-7.
  • 16. Saydam F, Değirmenci İ. Güneş HV. MikroRNA'lar ve kanser. Dicle Med J. 2011;38(1):113-120.
  • 17. Rudich A, Garzon R, Dorrance A. Non-Coding RNAs Are Implicit in Chronic Myeloid Leukemia Therapy Resistance. Int. J. Mol. Sci. 2022;23(20): 12271.
  • 18. Bansal M, Ansari S, Verma M. Role of miRNAs to control the progression of Chronic Myeloid Leukemia by their expression levels. Med Oncol. 2024;41(2):55.
  • 19. Seven M, Karatas OF, Duz MB, Ozen M. The role of miRNAs in cancer: from pathogenesis to therapeutic implications. Future Oncol. 2014;10(6):1027-1048.
  • 20. Fatica A, Bozzoni I. Role of microRNAs in hematological malignancies. Expert Rev Hematol. 2009;2(4): 415-423.
  • 21. Feng YH, Tsao CJ. Emerging role of microRNA-21 in cancer. Biomed Rep. 2016;5(4):395.
  • 22. Navabi A, Akbari B, Abdalsamadi M, Naseri S. The role of microRNAs in the development, progression and drug resistance of chronic myeloid leukemia and their potential clinical significance. Life Sci. 2022;296:120437.
  • 23. Moris VA, Zhang A, Yang T ve ark. MicroRNA-150 expression induces myeloid differentiation of human acute leukemia cells and normal hematopoietic progenitors. PLoS One. 2013;8(9):75815.
  • 24. Yeh CH, Moles R, Nicot C. Clinical significance of microRNAs in chronic and acute human leukemia. Mol Cancer. 2016;15(1):1-16.
  • 25. Zhao H, Wang D, Du W, Gu D, Yang R. MicroRNA and leukemia: tiny molecule, great function. Crit Rev Oncol Hematol. 2010;74(3):149-155.
  • 26. Kerscher EA, Slack FJ. Oncomirs-microRNAs with a role in cancer. Nat Rev Cancer. 2006;6(4):259-269.
  • 27. Yurt M, Ayyildiz O, Karakus A, Nursal AF, Isi H. MicroRNAs expression profiles as biomarkers and therapeutic tools in Turkish patients with chronic myeloid leukemia. Bratisl Lek Listy. 2020;121(2):159-163.
  • 28. Mirza MAB, Guru SA, Abdullah SM, Rizvi A, Saxena A. microRNA-21 expression as prognostic and therapeutic response marker in chronic myeloid leukaemia patients. Asian Pac J Cancer Prev. 2019;20(8):2379-2383.
  • 29. Pehlivan M. Kronik miyeloid lösemi (KML) hastalarında sFRP1 geninin promotör bölgesinin epigenetik ve genetik değişikliklerinin incelenmesi. Tıpta Uzmanlık Tezi. Dokuz Eylül Üniversitesi Tıp Fakültesi;2008.
  • 30. Srutova K, Curik N, Burda P, et al. BCR-ABL1 mediated miR-150 downregulation through MYC contributed to myeloid differentiation block and drug resistance in chronic myeloid leukemia. Haematologica. 2018;103(12):2016-2025.
  • 31. Fallah P, Amirizadeh N, Poopak B ve ark. Expression pattern of key micro RNA s in patients with newly diagnosed chronic myeloid leukemia in chronic phase. Int J Lab Hematol. 2015;37(4):560-568.
  • 32. Flamant S, Ritchie W, Guilhot J ve ark. Micro-RNA response to imatinib mesylate in patients with chronic myeloid leukemia. Haematologica. 2010;95(8):1325-1333.

Kronik Miyeloid Lösemi Hastaları’nda miR-21, miR-150, miR-155 Ekspresyon Düzeylerinin Araştırılması

Year 2025, Volume: 9 Issue: 1, 74 - 81, 21.04.2025
https://doi.org/10.46332/aemj.1327364

Abstract

Amaç: MikroRNA (miRNA)’lar proteinlere translasyonu gerçekleşmeyen, hücrede biyolojik mekanizmaları etkileyen RNA molekülleridir. miRNA ekspresyon düzeylerinin qPCR ile belirlenmesi KML hastalarının tedavisinin takibinde bilgi verebilir. Bu çalışmada KML hastalarının takibinde kullanılabilecek miR-21, miR-150, miR-155 ekspresyonlarının KML ile ilişkisi araştırılması amaçlanmıştır.

Araçlar ve Yöntem: Bu çalışma, imatinib, nilotinib, dasatinib ilaçlarıyla tedavi edilen 22 KML hastası ve 5 sağlıklı kontrolden elde edilen plazma örneklerinde yapıldı. Hasta ve kontrol periferik kan örneklerinden RNA ve miRNA eldesi Genaxxon miRNA pürifikasyon kiti kullanılarak gerçekleştirildi. Wiz ScriptcDNA Sentez Kiti kullanılarak cDNA eldesi yapıldı. cDNA örneklerinden hedeflenen miRNA ekspresyonlarının düzeyleri gerçek zamanlı PCR yöntemi ile analiz edildi.

Bulgular: Kontrol grubu miRNA ekspresyon düzeyleri 1.0 olarak belirlendi. KML yeni tanı grubunda miR-21 kat değişimi ortalama 0.6, miR-150 kat değişimi 0.3 ve miR-155 kat değişimi 0.5 bulundu. İmatinib tedavi grubunda miR-21, miR-150 ve miR-155 için kat değişimi sırasıyla 1.4, 0.5 ve 2.4 kat olarak bulundu. Nilotinib tedavi grubunda miR-21 düzeyi 3.5, miR-150 düzeyi 0.5 ve miR-155 düzeyi 4.3 bulundu. Dasatinib tedavi grubunda miR-21 kat değişimi 0.8, miR-150 kat değişimi 2.1 ve miR-155 kat değişimi 0.5 bulundu. Yapılan çalışmada miR-21 düzeyi ortalama 3.2, miR-150 düzeyi 1.0 ve miR-155 düzeyi 2.8 bulundu. miR-150 düzeyleri yeni tanı grubunda, İmatinib grubunda ve Nilotinib grubunda kontrol örneklerinden daha düşük oranda bulundu. Bu fark istatistiksel olarak yeni tanı grubunda (p=0.07484) ve Nilotinib grubunda (p=0.01541) anlamlıdır. Hasta ve kontroller arasında miR-21 ve miR-155 düzeyleri yönünden istatiksel olarak anlamlı bir farklılık bulunmadı.

Sonuç: Bu sonuçlar miRNA-150’nin KML hastalarının izleminde kullanılabileceğini ve ilaç direncinin erken dönemde tespitinde katkı sağlayabileceğini desteklemektedir.

Supporting Institution

Erciyes Üniversitesi Bilimsel Araştırma Projeleri

Project Number

TYL 2018-8012

Thanks

Araştırmamızı desteklekleyen Erciyes Üniversitesi Bilimsel Araştırma Projeleri koordinatörlüğüne; makalemizin kontrol ve düzeltmelerini yapan Prof. Dr. Halit Canatan hocamıza teşekkür ederim.

References

  • 1. Karaman A, Medeni ŞS, Sevindik ÖG ve ark. Kronik myeloid lösemi tanılı hastalarımızın retrospektif değerlendirilmesi. DEU Tıp Fak. Der. 2016;30(3):103-112.
  • 2. Goldman JM, Melo JV. Chronic myeloid leukemia advances in biology and new approaches to treatment. N Engl J Med. 2003;349(15):1451-1464.
  • 3. Sağ ŞÖ. Kronik Miyelositer Lösemilerde Füzyon Gen Kalitatif ve Kantitatif Değerlerinin FISH ve Moleküler Genetik Yöntemlerle Karşılaştırılması. Tıpta Uzmanlık Tezi, Bursa Uludag Üniversitesi; 2010.
  • 4. Di Bacco A, Keeshan K, McKenna SL, Cotter TG. Molecular abnormalities in chronic myeloid leukemia: deregulation of cell growth and apoptosis. Oncologist. 2000;5(5):405-415.
  • 5. Ali MA. Chronic Myeloid Leukemia in the Era of Tyrosine Kinase Inhibitors: An Evolving Paradigm of Molecularly Targeted Therapy. Mol Diagn Ther. 2016;20(4):315-333.
  • 6. Sun J, Hu R, Han M, et al. Mechanisms underlying therapeutic resistance of tyrosine kinase inhibitors in chronic myeloid leukemia. Int J Biol Sci. 2024;20(1): 175-181.
  • 7. Younes S, Ismail MA, Al-Jurf R, Ziyada A ve ark. Management of chronic myeloid leukaemia: current treatment options, challenges, and future strategies. Hematology. 2023;28(1):2196866.
  • 8. Krol J, Loedige I, Filipowicz W. The widespread regulation of microRNA biogenesis, function and decay. Nat Rev Genet. 2010;11(9):597-610.
  • 9. Almeida MI, Reis RM, Calin GA. MicroRNA history: discovery, recent applications, and next frontiers. Mutat Res. 2011;717(1-2):1-8.
  • 10. Wahid F, Shehzad A, Khan T, Kim YY. MicroRNAs: synthesis, mechanism, function, and recent clinical trials. Biochim Biophys Acta. 2010;1803(11):1231-1243.
  • 11. Reid G, Kirschner MB, Van Zandwijk N. Circulating microRNAs: Association with disease and potential use as biomarkers. Crit Rev Oncol Hematol. 2011;80(2):193-208.
  • 12. Etheridge A, Lee I, Hood L, ve ark. Extracellular microRNA: a new source of biomarkers. Mutat Res. 2011;717(1-2):85-90.
  • 13. Lujambio A and Lowe SW. The microcosmos of cancer. Nature. 2012;482(7385):347-355.
  • 14. Calin GA, Croce CM. MicroRNA signatures in human cancers. Nat Rev Cancer. 2006;6(11):857-866.
  • 15. Cho WC. OncomiRs: the discovery and progress of microRNAs in cancers. Mol Cancer. 2007;60(6):1-7.
  • 16. Saydam F, Değirmenci İ. Güneş HV. MikroRNA'lar ve kanser. Dicle Med J. 2011;38(1):113-120.
  • 17. Rudich A, Garzon R, Dorrance A. Non-Coding RNAs Are Implicit in Chronic Myeloid Leukemia Therapy Resistance. Int. J. Mol. Sci. 2022;23(20): 12271.
  • 18. Bansal M, Ansari S, Verma M. Role of miRNAs to control the progression of Chronic Myeloid Leukemia by their expression levels. Med Oncol. 2024;41(2):55.
  • 19. Seven M, Karatas OF, Duz MB, Ozen M. The role of miRNAs in cancer: from pathogenesis to therapeutic implications. Future Oncol. 2014;10(6):1027-1048.
  • 20. Fatica A, Bozzoni I. Role of microRNAs in hematological malignancies. Expert Rev Hematol. 2009;2(4): 415-423.
  • 21. Feng YH, Tsao CJ. Emerging role of microRNA-21 in cancer. Biomed Rep. 2016;5(4):395.
  • 22. Navabi A, Akbari B, Abdalsamadi M, Naseri S. The role of microRNAs in the development, progression and drug resistance of chronic myeloid leukemia and their potential clinical significance. Life Sci. 2022;296:120437.
  • 23. Moris VA, Zhang A, Yang T ve ark. MicroRNA-150 expression induces myeloid differentiation of human acute leukemia cells and normal hematopoietic progenitors. PLoS One. 2013;8(9):75815.
  • 24. Yeh CH, Moles R, Nicot C. Clinical significance of microRNAs in chronic and acute human leukemia. Mol Cancer. 2016;15(1):1-16.
  • 25. Zhao H, Wang D, Du W, Gu D, Yang R. MicroRNA and leukemia: tiny molecule, great function. Crit Rev Oncol Hematol. 2010;74(3):149-155.
  • 26. Kerscher EA, Slack FJ. Oncomirs-microRNAs with a role in cancer. Nat Rev Cancer. 2006;6(4):259-269.
  • 27. Yurt M, Ayyildiz O, Karakus A, Nursal AF, Isi H. MicroRNAs expression profiles as biomarkers and therapeutic tools in Turkish patients with chronic myeloid leukemia. Bratisl Lek Listy. 2020;121(2):159-163.
  • 28. Mirza MAB, Guru SA, Abdullah SM, Rizvi A, Saxena A. microRNA-21 expression as prognostic and therapeutic response marker in chronic myeloid leukaemia patients. Asian Pac J Cancer Prev. 2019;20(8):2379-2383.
  • 29. Pehlivan M. Kronik miyeloid lösemi (KML) hastalarında sFRP1 geninin promotör bölgesinin epigenetik ve genetik değişikliklerinin incelenmesi. Tıpta Uzmanlık Tezi. Dokuz Eylül Üniversitesi Tıp Fakültesi;2008.
  • 30. Srutova K, Curik N, Burda P, et al. BCR-ABL1 mediated miR-150 downregulation through MYC contributed to myeloid differentiation block and drug resistance in chronic myeloid leukemia. Haematologica. 2018;103(12):2016-2025.
  • 31. Fallah P, Amirizadeh N, Poopak B ve ark. Expression pattern of key micro RNA s in patients with newly diagnosed chronic myeloid leukemia in chronic phase. Int J Lab Hematol. 2015;37(4):560-568.
  • 32. Flamant S, Ritchie W, Guilhot J ve ark. Micro-RNA response to imatinib mesylate in patients with chronic myeloid leukemia. Haematologica. 2010;95(8):1325-1333.
There are 32 citations in total.

Details

Primary Language Turkish
Subjects ​Internal Diseases
Journal Section Original Articles
Authors

Hüseyin Avcılar 0000-0002-3871-9673

Hatice Altın 0009-0001-7603-6670

Sevil Şimşek 0000-0001-5998-6917

Leylagül Kaynar 0000-0002-2035-9462

Project Number TYL 2018-8012
Early Pub Date April 16, 2025
Publication Date April 21, 2025
Published in Issue Year 2025 Volume: 9 Issue: 1

Cite

APA Avcılar, H., Altın, H., Şimşek, S., Kaynar, L. (2025). Kronik Miyeloid Lösemi Hastaları’nda miR-21, miR-150, miR-155 Ekspresyon Düzeylerinin Araştırılması. Ahi Evran Medical Journal, 9(1), 74-81. https://doi.org/10.46332/aemj.1327364
AMA Avcılar H, Altın H, Şimşek S, Kaynar L. Kronik Miyeloid Lösemi Hastaları’nda miR-21, miR-150, miR-155 Ekspresyon Düzeylerinin Araştırılması. Ahi Evran Med J. April 2025;9(1):74-81. doi:10.46332/aemj.1327364
Chicago Avcılar, Hüseyin, Hatice Altın, Sevil Şimşek, and Leylagül Kaynar. “Kronik Miyeloid Lösemi Hastaları’nda MiR-21, MiR-150, MiR-155 Ekspresyon Düzeylerinin Araştırılması”. Ahi Evran Medical Journal 9, no. 1 (April 2025): 74-81. https://doi.org/10.46332/aemj.1327364.
EndNote Avcılar H, Altın H, Şimşek S, Kaynar L (April 1, 2025) Kronik Miyeloid Lösemi Hastaları’nda miR-21, miR-150, miR-155 Ekspresyon Düzeylerinin Araştırılması. Ahi Evran Medical Journal 9 1 74–81.
IEEE H. Avcılar, H. Altın, S. Şimşek, and L. Kaynar, “Kronik Miyeloid Lösemi Hastaları’nda miR-21, miR-150, miR-155 Ekspresyon Düzeylerinin Araştırılması”, Ahi Evran Med J, vol. 9, no. 1, pp. 74–81, 2025, doi: 10.46332/aemj.1327364.
ISNAD Avcılar, Hüseyin et al. “Kronik Miyeloid Lösemi Hastaları’nda MiR-21, MiR-150, MiR-155 Ekspresyon Düzeylerinin Araştırılması”. Ahi Evran Medical Journal 9/1 (April2025), 74-81. https://doi.org/10.46332/aemj.1327364.
JAMA Avcılar H, Altın H, Şimşek S, Kaynar L. Kronik Miyeloid Lösemi Hastaları’nda miR-21, miR-150, miR-155 Ekspresyon Düzeylerinin Araştırılması. Ahi Evran Med J. 2025;9:74–81.
MLA Avcılar, Hüseyin et al. “Kronik Miyeloid Lösemi Hastaları’nda MiR-21, MiR-150, MiR-155 Ekspresyon Düzeylerinin Araştırılması”. Ahi Evran Medical Journal, vol. 9, no. 1, 2025, pp. 74-81, doi:10.46332/aemj.1327364.
Vancouver Avcılar H, Altın H, Şimşek S, Kaynar L. Kronik Miyeloid Lösemi Hastaları’nda miR-21, miR-150, miR-155 Ekspresyon Düzeylerinin Araştırılması. Ahi Evran Med J. 2025;9(1):74-81.

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