Kronik Miyeloid Lösemili Hastaların CD34+ Hücrelerinde Gen İfade Profili

Abstract

Amaç: Kronik miyeloid lösemi (KML), hematopoietik kök hücrelerden kaynaklanan malign, klonal ve proliferatif bir hastalıktır. Bu çalışmanın amacı, KML’nin moleküler mekanizmalarını araştırmak için kronik fazdaki KML hastalarında rol oynayan potansiyel anahtar genleri ve yolakları belirlemek için biyoinformatik analiz yapmaktır. Gereç ve Yöntem: Biyoinformatik analiz için Gen Ekspresyonu Omnibus’u (GEO) veritabanından GSE5550 erişim numarasına sahip 9 KML hasta ve 8 sağlıklı bireyden alınan CD34+ hücrelerinin mRNA mikrodizin verileri indirildi. KML hastalarından alınan örneklerle sağlıklı bireylerden alınan örnekler farklı şekilde ifade edilen genleri (DEG) bulmak için GEO2R ile analiz edildi. DEG’ler için gen ontoloji ve Kyoto gen ve genom ansiklopedisi zenginleştirme analizleri ile protein-protein etkileşimi ağ analizi gerçekleştirildi ve KML ile ilişkili önemli genler belirlendi. Bulgular: GEO2R ile analiz sonrası p<0,01 ve log2FC<0, log2FC>0 olan DEG’ler seçildi. GSE5550 veri setinde KML hastalarında sağlıklı kontrol grubuna göre 1894 genin ifadesi artmış, 796 genin ifadesi azalmıştır. Sağlıklı kontrol grubuna göre KML hasta grubunda, farklı ifade edilen genlerin metabolik yolaklarda, RNA transportu, ribozom, endoplazmik retikulumda protein işlenmesi ve Ubiquitin aracılı proteoliz gibi yolaklarda zenginleştiği görülmüştür. Buna ilaveten RPL35, RPL39, RPS12, eEF1A1, RPLP1, RPL12, ODC1, PSMD7, USP14, PSMA1, GLI2, PSMC6 en önemli aday genler olarak belirlenmiştir. Sonuç: Çalışmamızın sonucu, ortaya çıkan genlerin ve yolakların lösemik kök hücreleri hedef alacak ve ilaç tedavisinde kullanılabilecek birer biyobelirteç adayı olabileceğini göstermiştir.

Keywords

• KML
• biyoinformatik analiz
• mikrodizin
• gen ifadesi

Kronik Miyeloid Lösemili Hastaların CD34+ Hücrelerinde Gen İfade Profili

Abstract

Objectives: Chronic myeloid leukaemia (CML) is a malignant, clonal and proliferative disease originating from haematopoietic stem cells. The aim of this study is to use bioinformatic analysis to identify potential key genes and pathways involved in CML patients in the chronic phase to investigate the molecular mechanisms of CML. Materials and Methods: For bioinformatic analysis, mRNA microarray data of CD34+ cells from 9 CML patients and 8 healthy individuals with accession number GSE5550 were downloaded from the Gene Expression Omnibus (GEO) database. Samples from CML patients and healthy individuals were analysed with GEO2R to find differentially expressed genes (DEGs). Gene ontology and Kyoto gene and genome encyclopedia enrichment analyses and protein-protein interaction network analysis were performed for DEGs and important CML related genes were identified. Results: After analysis with GEO2R, DEGs with p<0.01 and log2FC<0, log2FC>0 were selected. In the GSE5550 data set, the expression of 1894 genes increased and 796 genes decreased in CML patients compared to the healthy control group. It was observed that DEGs were enriched in pathways such as metabolic pathways, RNA transport, ribosome, protein processing in endoplasmic reticulum and Ubikitin-mediated proteolysis in the CML patient group in comparison to the healthy controls. In addition, RPL35, RPL39, RPS12, eEF1A1, RPLP1, RPL12, ODC1, PSMD7, USP14, PSMA1, GLI2, PSMC6 were identified as the most important candidate genes. Conclusion: The results of our study showed that the genes and pathways identified in our study may be biomarker candidates that can be used in drug treatment to target leukaemic stem cells.

Keywords

• CML
• bioinformatic analysis
• microarray
• gene expression

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