PTEN and AKT1 Variations in Childhood T-Cell Acute Lymphoblastic LeukemiaFulya Küçükcankurt1, Yücel Erbilgin2, Sinem Fırtına3, Özden Hatırnaz Ng4, Zeynep Karakaş5, Tiraje Celkan6, Ayşegül Ünüvar5, Uğur Özbek7, Müge Sayitoğlu21İstanbul University, Aziz Sancar Institute of Experimental Medicine, Department of Genetics, Istanbul, Turkey; Altınbaş University, Faculty of Medicine, Istanbul, Turkey
2İstanbul University, Aziz Sancar Institute of Experimental Medicine, Department of Genetics, Istanbul, Turkey
3İstanbul University, Aziz Sancar Institute of Experimental Medicine, Department of Genetics, Istanbul, Turkey; İstinye University, Faculty of Art and Science, Department of Molecular Biology and Genetics, İstanbul, Turkey
4İstanbul University, Aziz Sancar Institute of Experimental Medicine, Department of Genetics, Istanbul, Turkey; Acıbadem Mehmet Ali Aydınlar University School of Medicine, Department of Medical Biology, Istanbul, Turkey
5İstanbul University, School of Medicine, Department of Pediatrics Hematology, Istanbul, Turkey
6Istanbul University-Cerrahpaşa School of Medicine, Department of Pediatrics Hematology, Istanbul, Turkey
7İstanbul University, Aziz Sancar Institute of Experimental Medicine, Department of Genetics, Istanbul, Turkey; Acıbadem Mehmet Ali Aydınlar University School of Medicine, Department of Medical Genetics, Istanbul, Turkey
Objective: PTEN/AKT pathway deregulations have been reported to be associated with treatment response in acute leukemia. This study examined pediatric T-cell acute lymphoblastic leukemia (T-ALL) samples for PTEN and AKT1 gene variations and evaluated the clinical findings.
Materials and Methods: Fifty diagnostic bone marrow samples of childhood T-ALL cases were investigated for the hotspot regions of the PTEN and AKT1 genes by targeted next-generation sequencing.
Results: A total of five PTEN variations were found in three of the 50 T-ALL cases (6%). Three of the PTEN variations were first reported in this study. Furthermore, one patient clearly had two different mutant clones for PTEN. Two intronic single-nucleotide variations were found in AKT1 and none of the patients carried pathogenic AKT1 variations.
Conclusion: Targeted deep sequencing allowed us to detect both lowlevel variations and clonal diversity. Low-level PTEN/AKT1 variation frequency makes it harder to investigate the clinical associations of the variants. On the other hand, characterization of the PTEN/ AKT signaling members is important for improving case-specific therapeutic strategies.
Keywords: T-ALL, PTEN, AKT1, Next-generation sequencing
Çocukluk Çağı T-hücreli Akut Lenfoblastik Lösemi Hastalarında PTEN ve AKT1 VaryasyonlarFulya Küçükcankurt1, Yücel Erbilgin2, Sinem Fırtına3, Özden Hatırnaz Ng4, Zeynep Karakaş5, Tiraje Celkan6, Ayşegül Ünüvar5, Uğur Özbek7, Müge Sayitoğlu21İstanbul University, Aziz Sancar Institute of Experimental Medicine, Department of Genetics, Istanbul, Turkey; Altınbaş University, Faculty of Medicine, Istanbul, Turkey
2İstanbul University, Aziz Sancar Institute of Experimental Medicine, Department of Genetics, Istanbul, Turkey
3İstanbul University, Aziz Sancar Institute of Experimental Medicine, Department of Genetics, Istanbul, Turkey; İstinye University, Faculty of Art and Science, Department of Molecular Biology and Genetics, İstanbul, Turkey
4İstanbul University, Aziz Sancar Institute of Experimental Medicine, Department of Genetics, Istanbul, Turkey; Acıbadem Mehmet Ali Aydınlar University School of Medicine, Department of Medical Biology, Istanbul, Turkey
5İstanbul University, School of Medicine, Department of Pediatrics Hematology, Istanbul, Turkey
6Istanbul University-Cerrahpaşa School of Medicine, Department of Pediatrics Hematology, Istanbul, Turkey
7İstanbul University, Aziz Sancar Institute of Experimental Medicine, Department of Genetics, Istanbul, Turkey; Acıbadem Mehmet Ali Aydınlar University School of Medicine, Department of Medical Genetics, Istanbul, Turkey
Amaç: PTEN/AKT yolak düzensizliklerinin akut lösemide tedavi yanıtı ile ilişkili olduğu bildirilmiştir. Çalışmanın kapsamı, pediatrik T-ALL hastalarının PTEN ve AKT1 genlerinin sıcak bölge varyasyonları için incelenmesi ve klinik bulgularla değerlendirilmesidir.
Gereç ve Yöntem: Elli pediatrik T-ALL olgusunun tanı zamanı kemik iliği örnekleri, PTEN ve AKT1 genlerinin sıcak bölgeleri için hedefe yönelik yeni nesil dizileme ile dizilenmiştir.
Bulgular: Elli T-ALL olgusunun %6’sında PTEN varyasyonu saptanmıştır. Tespit edilen varyasyonlardan üçü ilk defa bu çalışmada gösterilmiştir. Ayrıca bir hastanın PTEN açısından iki farklı mutant klon taşıdığı belirlenmiştir. AKT1 geninde iki intronik tek nükleotid polimorfizmi tespit edilirken hiçbir olguda patojenik AKT1 varyasyonu saptanmamıştır.
Sonuç: Derin dizileme, hem düşük düzeydeki varyasyonların hem de klonal çeşitliliğin belirlenmesine olanak sağlamıştır. T-ALL hastalarındaki düşük düzey PTEN/AKT1 varyasyon sıklığı, varyantların klinikle ilişkisinin ortaya çıkarılmasını zorlaştırmaktadır. Diğer yandan, PTEN/AKT sinyal yolağının karakterizasyonu hasta spesifik terapötik stratejilerin uygulanabilirliği için önemlidir.
Anahtar Kelimeler: T-ALL, PTEN, AKT1, Yeni nesil dizileme
Fulya Küçükcankurt, Yücel Erbilgin, Sinem Fırtına, Özden Hatırnaz Ng, Zeynep Karakaş, Tiraje Celkan, Ayşegül Ünüvar, Uğur Özbek, Müge Sayitoğlu. PTEN and AKT1 Variations in Childhood T-Cell Acute Lymphoblastic Leukemia. Turk J Hematol. 2020; 37(2): 98-103
Corresponding Author: Müge Sayitoğlu |
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