KML VE KML LÖSEMİK KÖK HÜCRESİ ARASINDA MİKRORNA EKSPRESYON DEĞİŞİMLERİNİN DEĞERLENDİRİLMESİ

Year 2020, , 315 - 321, 01.09.2020

Melek Pehlivan Mustafa Soyöz , Hatice İlayhan Karahan Çöven Burcu Çerçi Tülay Kılıçaslan Ayna , Halil Ateş Zeynep Yüce Hakkı Ogün Sercan

https://doi.org/10.17343/sdutfd.624530

Abstract

Amaç:
Kronik Miyeloid Lösemi (KML), hematopoetik kök hücreden (HKH) köken alan miyeloproliferatif
bir hastalıktır. MikroRNA'lar, transkripsiyon
sonrası gen ekspresyonunu düzenlenleyen küçük kodlamayan RNA’lardır. miRNA’lar KML’nin progresyonunda,  lösemik kök hücre büyümesi ve tirozin kinaz
inhibitörü (TKİ) direncinin gelişmesinde hücre homeostazisini
etkilemektedirler. Bu çalışmada KML lösemik hücresi ve KML lösemik kök hücresi
(LKH) arasında değişen miRNA ekspresyon profillerinin incelenmesi amaçlanmıştır.

Gereç
ve yöntem: KML hücre hattı olan K562 hücrelerinden,
manyetik hücre ayrımlama (MACS) yöntemi kullanılarak
CD34⁺CD38^- lösemik kök hücreleri ayrımlanmıştır.
Ayrımlanan LKH’lerin saflığının %85-92 arasında olduğu akım sitometri yöntemi
ile gösterilmiştir. K562 ve K562 LKH’leri arasında, gerçek zamanlı kantitatif
PCR ile kanser kök hücre ilişkili 84 adet miRNA’nın ekspresyon değişimleri
incelenmiştir.

Bulgular:
K562 ve K562 LKH’leri arasında, kök hücre ilişkili olduğu bilinen 84 adet miRNA’dan 7’sinin anlamlı
düzeyde değiştiğini gözledik (P<0,05). 
K562 LKH’lerinde hsa-miR-29b-3p’nin ekspresyon düzeylerinde artış izlenirken; hsa-miR-320d,  hsa-miR-96-5p,
hsa-let-7e-5p, hsa-miR-17-5p, hsa-miR-181b-5p hsa-miR-423-5p’da azalma olduğu gözlenmiştir.

Sonuç
: KML lösemik hücreleri ile KML LKH’leri arasında proliferasyon,
eritroid farklılaşma, kendi kendini yenileme ve apoptoz sürecinde rol alan
miRNA’lar ve hedef genlerinin ekspresyonlarındaki
değişim, hastalığın ilerlemesinde
miRNA’larında rol oynayabileceğini
göstermektedir. Bu nedenle KML LKH’lerine
özgü miRNA’ların hastalığın
progresyonunun ve TKI direncinin önlenmesi
için yeni terapötik stratejilerin geliştirilmesinde hedef
moleküller olabileceğini düşünmekteyiz.

Keywords

Kronik Myeloid Lösemi, Lösemik Kök Hücre, mikroRNA

Supporting Institution

İzmir Katip Çelebi Üniversitesi Bilimsel Araştırma Projeleri Koordinatörlüğü

Project Number

2016.ÖNP.SHMY.0026

Thanks

Bu çalışma 2016.ÖNP.SHMY.0026 proje numarası ile İzmir Katip Çelebi Üniversitesi Bilimsel Araştırma Projeleri Koordinatörlüğü tarafından desteklenmiştir.

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