Pediatrik Philadelphia benzeri akut lenfoblastik lösemilerin biyolojisi
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Date
2019-09-19
Authors
Efendi, Ecem
Journal Title
Journal ISSN
Volume Title
Publisher
Bursa Uludağ Üniversitesi
Abstract
Philadelphia (Ph) benzeri akut lenfoblastik lösemi (ALL), yüksek risk sınıflamasında yer alan ve kötü prognoz gösteren B- hücreli akut lenfoblastik löseminin (B-ALL) alt grubudur. Gen ekspresyon profili olarak Ph pozitif ALL'ye benzemektedir, ancak bu alt tipte BCR-ABL1 füzyonu mevcut değildir. Hastalık genetik olarak heterojendir. Ayrıca, etnik kökenleri farklı olan Ph benzeri ALL vakalarının genetik değişimleri de farklılık göstermektedir. Ph benzeri ALL vakalarının B-ALL'li hastalar arasından ayırt edilerek sınıflandırılabilmesi etkin tedavi almaları için önemlidir. Son yıllarda, Ph benzeri ALL alt grubuna ait vakaların tanımlanması için, B-ALL vakalarında genetik ve klinik bulgular değerlendirilmesinin yanısıra, gen ifade farklılıklarının analiz edildiği panellerin tasarlanması gündemdedir. Bu amaçla, Ph benzeri grubun tanımlanabilmesi için Bursa Uludağ Üniversitesi Çocuk Hematoloji AD.'na başvuran hastalar arasından Ph pozitif ve Ph negatif vakalar projeye dahil edildi. Mevcut tez çalışması dahilinde; Türk popülasyonuna özgü, Ph benzeri ALL vakalarının tanımlanmasında kullanılacak gen panelinin oluşturulması amaçlanmıştır. 23 kemik iliği materyali ile gerçekleştirilen RNA izolasyonu sonrasında RT-qPCR yöntemi ile mRNA gen ekspresyon profilleri analiz edildi. Çalışma dahilinde hazırlanan custom mRNA gen paneli içerisinde 96 gen değerlendirildi ve kontrol örneği ile benzer ifadeye sahip 36 gen, Ph benzeri ALL vakalarının tanımlanmasında biyobelirteç paneli olabileceği öngörüldü. Mevcut çalışmada, pediatrik B-ALL'li hastalar arasında yer alan Ph benzeri alt gruba ait hastaların gen profillerinin belirlenmesi ile ön ayırıcı tanı gerçekleştirildi. İleri analizler sonucunda; Türk popülasyonuna ait gen paneli ile tanımlanan Ph benzeri ALL alt grubunun tedavi protokollerine hedefe yönelik tirozin kinaz inhibitörlerinin ilave edilmesi sağlanarak prognozun iyileştirilmesi ve sağkalım oranlarının yükseltilmesine katkı sağlanacaktır.
Biology of Pediatric Philadelphia-like Acute Lymphoblastic Leukemia Philadelphia-like acute lymphoblastic leukemia is a subgroup of B-ALL with high-risk classification and poor prognosis. The gene expression profile is similar to Philadelphia positive acute lymphoblastic leukemia, but this subtype does not have BCR-ABL1 fusion. The disease is genetically heterogeneous. Besides, genetic alterations of Ph-like ALL cases with different ethnic backgrounds differ. It is important that ph-like ALL cases can be classified and differentiated from B-ALL patients to receive effective treatment. In recent years, to identify cases of the Ph-like ALL subgroup, in addition to the evaluation of genetic and clinical findings in B-ALL cases, the design of panels in which gene expression differences are analyzed is on the agenda. For this purpose, to identify the Ph-like group, Ph-positive and Ph negative cases were included in the project among the patients who applied to Bursa Uludağ University Department of Pediatric Hematology. Within the current thesis; This study aimed to establish a gene panel to be used to identify Ph-like ALL cases specific to the Turkish population. After RNA isolation with 23 bone marrow materials, mRNA gene expression profiles were analyzed by RT-qPCR method. In the custom mRNA gene panel prepared within the study, 96 genes were evaluated and 36 genes with a similar expression as the control group could be a biomarker panel may be used to identify cases of Ph-like ALL. In the present study, a pre-differential diagnosis was made by determining the gene profiles of the Ph-like subgroup among the pediatric B-ALL patients. As a result of advanced analysis; By adding targeted tyrosine kinase inhibitors to the treatment protocols of the Ph-like ALL subgroup defined by the gene panel of the Turkish population, it will contribute to improve the prognosis and increase survival rates.
Biology of Pediatric Philadelphia-like Acute Lymphoblastic Leukemia Philadelphia-like acute lymphoblastic leukemia is a subgroup of B-ALL with high-risk classification and poor prognosis. The gene expression profile is similar to Philadelphia positive acute lymphoblastic leukemia, but this subtype does not have BCR-ABL1 fusion. The disease is genetically heterogeneous. Besides, genetic alterations of Ph-like ALL cases with different ethnic backgrounds differ. It is important that ph-like ALL cases can be classified and differentiated from B-ALL patients to receive effective treatment. In recent years, to identify cases of the Ph-like ALL subgroup, in addition to the evaluation of genetic and clinical findings in B-ALL cases, the design of panels in which gene expression differences are analyzed is on the agenda. For this purpose, to identify the Ph-like group, Ph-positive and Ph negative cases were included in the project among the patients who applied to Bursa Uludağ University Department of Pediatric Hematology. Within the current thesis; This study aimed to establish a gene panel to be used to identify Ph-like ALL cases specific to the Turkish population. After RNA isolation with 23 bone marrow materials, mRNA gene expression profiles were analyzed by RT-qPCR method. In the custom mRNA gene panel prepared within the study, 96 genes were evaluated and 36 genes with a similar expression as the control group could be a biomarker panel may be used to identify cases of Ph-like ALL. In the present study, a pre-differential diagnosis was made by determining the gene profiles of the Ph-like subgroup among the pediatric B-ALL patients. As a result of advanced analysis; By adding targeted tyrosine kinase inhibitors to the treatment protocols of the Ph-like ALL subgroup defined by the gene panel of the Turkish population, it will contribute to improve the prognosis and increase survival rates.
Description
Keywords
Philadelphia benzeri akut lenfoblastik lösemi, Pediatrik, Gen ekspresyonu, RT-qPCR, Philadelphia-like, Acute lymphoblastic leukemia, Pediatric, Gene expression, RT-qPCR
Citation
Efendi, E. (2019). Pediatrik Philadelphia benzeri akut lenfoblastik lösemilerin biyolojisi. Yayınlanmamış yüksek lisans tezi. Bursa Uludağ Üniversitesi Sağlık Bilimleri Enstitüsü.