HDAC2, HDAC4, HDAC5, HDAC7, HDAC8, HDAC9 Gen İfade Seviyelerinin Çocukluk Çağı Akut Lösemilerinde Prognoz İle İlişkisi

Abstract

Amaç: Histon deasetilazların değişmiş ifadesi hematolojik maligniteler için kanser tedavisinde hedef olabilecek niteliktedir. HDAC mutasyonları ve anormal ifade seviyeleri çeşitli kanser tiplerinde ve özellikle hematolojik malignitelerde sıklıkla görülmekte olduğu, çocukluk çağı lösemi örneklerinde HDAC2, HDAC3, HDAC6, HDAC7 ve HDAC8 gen ifadelerinin sağlıklı çocuk kemik iliği örneklerine göre önemli derece yüksek olduğu rapor edilmiştir.

Gereç ve Yöntem: Çalışmamızda 6 HDAC geninin gen ifade profilini çocukluk çağı akut lösemisinde kantitatif Real Time PCR yöntemi kullanılması ile tedavinin farklı zamanlarında belirlenmesi gerçekleştirilmiştir.

Bulgular: Çalışmamız sonucunda çocukluk çağı lösemi örneklerinde HDAC genleri ifade seviyelerinin birbirine göre farklılık gösterdiği gözlenmiştir. Çalışmamızda; tedavi öncesinde, kontrol örneklerinin ifadelenme seviyelerine göre; HDAC2 ve HDAC9 ifadelenme seviyelerinin düşük, HDAC 4 ve HDAC 8 eşit seviyede ve son olarak HDAC 5 ve HDAC7 yüksek olduğu belirlenmiştir. Tedavi sonrasında ise,  kontrol örneklerinin ifadelenme seviyelerine göre; HDAC2 ve HDAC9 ifadelenme seviyelerinin düşük, HDAC 4 ve HDAC 8 yükseldiği ve HDAC 5 ve HDAC7’nin ise düştüğü tespit edilmiştir.

Sonuçlar: Tümor gelişiminde rol oynayan genlerin ve/veya yolakları kontrol eden HDAC gen seviyelerinin artması, tedavi sonrasında ise bu ifadelenme seviyelerinin sağlıklı örneklerin seviyesine eşit olması, HDAC genlerinin kanser patogenezi ile direkt ilişkide olabileceğini düşündürmektedir.

Keywords

• Histondeasetilaz
• lösemi
• gen ifadesi

HDAC2, HDAC4, HDAC5, HDAC7, HDAC8, HDAC9 Gene Expression Levels Associated with Prognosis in Childhood Acute Leukemia

Abstract

Objective: HDAC have been frequently observed in several types of cancers, including haematological malignancies. Altered expression of HDACs and mutations are common feature in several human malignancies and may represent an interesting target for cancer treatment, including haematological malignancies. HDAC2, HDAC3, HDAC6, HDAC7 and HDAC8 gene expressions in childhood leukemia cases were reported to be significantly higher than in healthy pediatric bone marrow samples. This study aims evaluting the gene expressions of HDACs in different types of childhood leukemia. Material and Methods: In our study, identification and comparation with reference gene of 6 HDAC genes were performed at before and after treatment in 13 patients with acute childhood leukemia samples using quantitative Real-Time PCR Results: As a result of our study, it was observed that expression levels of HDAC genes in childhood leukemia were different according to each other. In our study; according to the level of expression of patients samples to control samples before treatment; HDAC2 and HDAC9 expression levels are low, HDAC 4 and HDAC 8 are equal, and finally HDAC 5 and HDAC7 are high. After treatment, according to the expression levels of patients samples to control samples; It has been found that HDAC2 and HDAC9 rendering levels are low, HDAC 4 and HDAC 8 are rising, and HDAC 5 and HDAC 7 are falling. Conclusions: The elevation of HDAC gene levels controlling genes and / or pathways involved in tumor development and the equivalence of these expression levels to that of healthy specimens after treatment suggests that HDAC genes may be directly related to cancer pathogenesis. 

Keywords

• Histone deacetylases
• leukemia
• gene expression
• epigenetic mechanism

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