PTEN and AKT1 Gene Expression Levels in Childhood T-ALL Patients

Abstract

Objective: Impaired activation of the PI3K/AKT signaling pathway has been associated with tumor development. The PTEN/AKT pathway plays a critical role in cell growth and survival and has been associated with chemotherapy resistance in leukemia. In this study, PTEN and AKT1 gene expression were determined in childhood T-ALL patients, and the effect was investigated on the prognosis of the disease. Materials and Methods: Bone marrow samples from 39 childhood cases were obtained at the time of diagnosis and screened with real-time quantitative PCR for PTEN and AKT1 genes. Results: In our study, no difference between T-ALL patients compared to controls was observed in PTEN gene expression whereas AKT1 gene expression was significantly increased (p<0.0001). There was no significant relationship between gene expression and clinical features of the patients, overall and disease-free survival rates while induction therapy-related survival analyzes revealed a significant relationship between PTEN and AKT1 gene expression and overall survival rates (p=0.026 and p=0.034 Cox regression analysis, respectively). Conclusion: In our study, the presence of increased AKT1 gene expression was demonstrated in T-ALL patients independent of PTEN expression. Future studies will reveal whether it will be a suitable candidate for targeted therapies.

Keywords

• T-cell acute lymphoblastic leukemia
• gene expression
• PTEN
• AKT1

Project Number

BAP Proje No: 48185 ve İstanbul Kalkınma Ajansı Proje No: TR10/15/YNK/0093

Çocukluk Çağı T-ALL Hastalarında PTEN ve AKT1 Gen Anlatım Düzeyleri

Abstract

Amaç: PI3K/AKT sinyal yolağının bozulmuş aktivasyonu tümör gelişimi ile ilişkilendirilmiştir. PTEN/AKT yolağı, hücre büyümesi ve sağ kalımında kritik role sahip olup, lösemilerde kemoterapi direnci ile ilişkilendirilmiştir. Bu çalışma kapsamında, çocukluk çağı T-ALL hastalarındaki PTEN ve AKT1 gen anlatımları belirlendi ve hastalığın prognozuna olan etkisi araştırıldı. Gereç ve Yöntem: Otuz dokuz çocukluk çağı T-ALL olgusunun, tanı zamanı kemik iliği örnekleri kantitatif gerçek zamanlı PZR ile PTEN ve AKT1 genleri için tarandı. Gen anlatım düzeylerinin hastaların yaş, cinsiyet, immünfenotip, tedavi yanıtı, nüks ve sağ kalım gibi klinik verileri ile ilişkisi incelendi. Bulgular: Çalışmamızda, T-ALL hastalarında PTEN gen anlatımında kontrollere göre bir farklılık gözlenmezken, AKT1 gen anlatımının anlamlı düzeyde arttığı belirlendi (p<0,0001). Hastaların klinik özellikleri, genel ve hastalıksız sağ kalım oranları ve gen anlatım düzeyleri arasında anlamlı bir ilişki saptanmazken, indüksiyon tedavi ilişkili sağ kalım analizleri PTEN ve AKT1 gen anlatımları ile genel sağ kalım oranları arasında (sırasıyla, p=0,026 ve p=0,034 Cox regresyon analizi) anlamlı bir ilişki ortaya koyuldu. Diğer klinik parametreler ile gen anlatım düzeyleri arasında anlamlı ilişki saptanmadı. Sonuç: Çalışmamızda, T-ALL örneklerinde PTEN gen anlatımından bağımsız olarak artmış AKT1 gen anlatımının varlığı ve sağ kalım sürelerini etkilediğine dair bulgular elde edildi. Gelecekteki çalışmalar, AKT1’in hedefe yönelik tedaviler için uygun bir aday olup olmayacağını ortaya çıkaracaktır.

Keywords

• T-hücreli Akut Lenfoblastik Lösemi
• Gen Anlatımı
• PTEN
• AKT1

Supporting Institution

İstanbul Üniversitesi Bilimsel Araştırma Projeleri Birimi ve İstanbul Kalkınma Ajansı, Geleceğe Yatırım: BİYOBANKA projesi

Project Number

BAP Proje No: 48185 ve İstanbul Kalkınma Ajansı Proje No: TR10/15/YNK/0093

Thanks

Hasta materyallerinin sağlanmasındaki katkılarından dolayı Prof. Dr. Zeynep Karakaş ve Prof. Dr. Tiraje Çelkan’a teşekkür ederiz.

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