Kronik myeloid lösemi hastalarında hipofiz tümörü transforme edici gen (PTTG) ekspresyonunun değerlendirilmesi
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Tarih
2019
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Yayıncı
Necmettin Erbakan Üniversitesi Sağlık Bilimleri Enstitüsü
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Kronik myeloid Lösemi (KML) pluripotent hematopoetik kök hücrenin malign transformasyonu sonucu gelişen klonal bir kök hücre hastalığıdır. KML olgularının %95'de t(9;22)(q34;q11) translokasyonu sonucu lösemik fenotipin gelişmesinden sorumlu BCR-ABL1 füzyon proteini oluşmaktadır. BCR/ABL1füzyon proteiniyle karakterize olan KML, erişkinlerdeki lösemilerin yaklaşık %20'sini oluşturmaktadır. KML etiyolojisinden sorumlu tutulabilecek herhangi bir çevresel etken bilinmemekle birlikte iyonize radyasyona maruz kalmanın KML riskini arttırdığı rapor edilmiştir. KML'nin klinik seyri laboratuvar bulguları ve klinik karakteristiklerine göre üç ayrı evreye ayrılır: kronik evre, akselere evre ve blastik evredir. KML tanısı, periferik kan yayması ve kemik iliği incelemesi ile birlikte karyotip analizinde Ph kromozomu varlığının veya floresan insituhibridizasyon (FISH) ya da polimeraz zincir reaksiyonu (PCR) yöntemi ile BCR-ABL1 füzyon geninin saptanması ile konur. Sitogenetik analiz ile hastaların yaklaşık olarak %95' inde Ph kromozomu saptanır. Sitogenetik analiz ile Ph kromozomu saptanmayan KML hastalarının çoğunda moleküler tekniklerle translokasyon saptanabilir. Ph kromozomu üzerinde oluşan BCR-ABL1 füzyon geni, hücre içinde birçok yolağı aktive eden bir tirozin kinazı kodlar. Hipofiz Tümörü Transforme Edici Gen (Pituitary Tumor Transforming Gene-PTTG) gen, sıçan hipofiz tümörü hücrelerinden 1997 yılında izole edildi . PTTG'nin birincil fonksiyonu, kardeş kromatidlerin zıt kutuplara iğ iplikleri ile ayrılmasının kontrolü ile ilgilidir. Bu aktiviteye göre, kromozomun hatalı ayrılmasının bir sonucu olarak genomik dengesizlik, upregüle PTTG ekspresyonunun onkojenik potansiyelinin sebebini açıklayabilir. PTTG'in aşırı ekspresyonu anöploidi jenerasyonu ile ilişkilidir, bu durum multiple tümör tiplerindeki farklalaşmış prognoz ile korelasyon gösterir. Çalışmada, RNA izolasyonu ve RT-PCR analizi kullanılarak 129 numune üzerinden değerlendirme yapıldı. BCR/ABL1 trasnkripti pozitif olan 88 adet hasta numunesi ile BCR/ABL1 trasnkripti negatif olan 41 adet hasta numunesi arasındaki PTTG gen ekspresyonu değerlendirilmiştir. Analiz sonuçları değerlendirildiğinde, negatif ve pozitif transkript örnekleri arasında PTTG gen ekspresyonunun farklılık gösterdiği gözlenmiştir. BCR/ABL1 trasnkripti pozitif olan numunelerde PTTG ekspresyonunun arttığı tespit edilmiştir. KML deki klinik seyirin ek kromozom anomalilerle ilişkisi göz önüne alındığında PTTG ekspresyonunun KML'de değerlendirilmesinin önemli olabileceğini ön görüldü. Bu çalışmada, KML hastalarında PTTG ekspresyonunun hasta prognozu ile ilişkili olup olmadığını değerlendirmek amaçlandı
Chronic myeloid leukemia (CML) is a clonal stem cell disease caused by malignant transformation of a pluripotent hematopoietic stem cell BCR-ABL1 fusion protein is responsible for the development of leukemic phenotype as a result of t (9; 22) (q34; q11) translocation in 95% of CML cases. CML, be characterized by the BCR / ABL1 fusion protein, constitutes for about 20% of leukemias in adults. Although there are no known environmental factors responsible for the etiology of CML, exposure to ionizing radiation has been reported to increase the risk of CML. According to the clinical course and laboratory findings of CML is divided into three different phases: chronic phase, accelerated phase and blastic phase. The diagnosis of CML is made by peripheral blood smear and bone marrow examination with detecting the presence of the Ph chromosome in the karyotype analysis, or by the detection of the BCR-ABL1 fusion gene by fluorescence insitu hybridization (FISH) or polymerase chain reaction (PCR). Ph-chromosome is detected in approximately 95 % of the patients by cytogenetic analysis. Most CML patients without Ph-chromosome in cytogenetic analysis can detect translocation by molecular techniques The BCR-ABL1 fusion gene formed on the Ph chromosome, encodes a tyrosine kinase that activates many pathways within the cell. Pituitary Tumor Transforming Gene (PTTG) gene was isolated from rat pituitary tumor cells in 1997. PTTG1 primary function is related to the control of sister chromatid separation to the opposite spindle poles. According to this activity, genomic imbalance as a result of chromosome missegregation is a rationale for the oncogenic potential of upregulated PTTG1 expression. In fact, PTTG1 over-expression has been associated with aneuploidy generation, what correlates with a differentiated prognosis in multiple tumor types . In this study, 129 samples were evaluated using RNA isolation and RT-PCR analysis. PTTG gene expression was evaluated between 88 patient samples with positive BCR / ABL1 transcript and 41 patient samples with negative BCR / ABL1 transcript. When the analysis results were evaluated, it was observed that PTTG gene expression differed between negative and positive transcript samples. PTTG expression was found to be increased in samples with positive BCR / ABL1 transcript. Considering the relationship between clinical course and additional chromosomal abnormalities in CML, it was predicted that evaluation of PTTG expression in CML may be important. In this study, we aimed to evaluate whether PTTG expression is associated with patient prognosis in CML patients.
Chronic myeloid leukemia (CML) is a clonal stem cell disease caused by malignant transformation of a pluripotent hematopoietic stem cell BCR-ABL1 fusion protein is responsible for the development of leukemic phenotype as a result of t (9; 22) (q34; q11) translocation in 95% of CML cases. CML, be characterized by the BCR / ABL1 fusion protein, constitutes for about 20% of leukemias in adults. Although there are no known environmental factors responsible for the etiology of CML, exposure to ionizing radiation has been reported to increase the risk of CML. According to the clinical course and laboratory findings of CML is divided into three different phases: chronic phase, accelerated phase and blastic phase. The diagnosis of CML is made by peripheral blood smear and bone marrow examination with detecting the presence of the Ph chromosome in the karyotype analysis, or by the detection of the BCR-ABL1 fusion gene by fluorescence insitu hybridization (FISH) or polymerase chain reaction (PCR). Ph-chromosome is detected in approximately 95 % of the patients by cytogenetic analysis. Most CML patients without Ph-chromosome in cytogenetic analysis can detect translocation by molecular techniques The BCR-ABL1 fusion gene formed on the Ph chromosome, encodes a tyrosine kinase that activates many pathways within the cell. Pituitary Tumor Transforming Gene (PTTG) gene was isolated from rat pituitary tumor cells in 1997. PTTG1 primary function is related to the control of sister chromatid separation to the opposite spindle poles. According to this activity, genomic imbalance as a result of chromosome missegregation is a rationale for the oncogenic potential of upregulated PTTG1 expression. In fact, PTTG1 over-expression has been associated with aneuploidy generation, what correlates with a differentiated prognosis in multiple tumor types . In this study, 129 samples were evaluated using RNA isolation and RT-PCR analysis. PTTG gene expression was evaluated between 88 patient samples with positive BCR / ABL1 transcript and 41 patient samples with negative BCR / ABL1 transcript. When the analysis results were evaluated, it was observed that PTTG gene expression differed between negative and positive transcript samples. PTTG expression was found to be increased in samples with positive BCR / ABL1 transcript. Considering the relationship between clinical course and additional chromosomal abnormalities in CML, it was predicted that evaluation of PTTG expression in CML may be important. In this study, we aimed to evaluate whether PTTG expression is associated with patient prognosis in CML patients.
Açıklama
Yüksek Lisans Tezi
Anahtar Kelimeler
Kronik Myeloid Lösemi, PTTG Ekspresyonu, RT-PCR, Chronic Myeloid Leukemia, PTTG Expression, RT-PCR
Kaynak
WoS Q Değeri
Scopus Q Değeri
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Künye
Gençer Çelikel, M. (2019). Kronik myeloid lösemi hastalarında hipofiz tümörü transforme edici gen (PTTG) ekspresyonunun değerlendirilmesi. (Yayımlanmamış Yüksek Lisans Tezi). Necmettin Erbakan Üniversitesi, Sağlık Bilimleri Enstitüsü Genetik Anabilim Dalı, Konya.
