Prognostic evidence of LEF1 isoforms in childhood acute lymphoblastic leukemia
Yucel Erbilgin
Department of Genetics, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey
Search for more papers by this authorOzden Hatirnaz Ng
Department of Genetics, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey
Faculty of Medicine, Department of Medical Biology, Acibadem Mehmet Ali Aydinlar University, Istanbul, Turkey
Search for more papers by this authorIsmail Can
Institute of Health Sciences, Istanbul University, Istanbul, Turkey
Search for more papers by this authorSinem Firtina
Institute of Health Sciences, Istanbul University, Istanbul, Turkey
Faculty of Art and Science, Department of Molecular Biology and Genetics, Istinye University, İstanbul, Turkey
Search for more papers by this authorFulya Kucukcankurt
Institute of Health Sciences, Istanbul University, Istanbul, Turkey
Faculty of Medicine, Altınbaş University, Istanbul, Turkey
Search for more papers by this authorSerap Karaman
Istanbul Faculty of Medicine, Pediatric Hematology Oncology Department, Istanbul University, Istanbul, Turkey
Search for more papers by this authorZeynep Karakas
Istanbul Faculty of Medicine, Pediatric Hematology Oncology Department, Istanbul University, Istanbul, Turkey
Search for more papers by this authorTulin Tiraje Celkan
Pediatric Hematology Oncology Department, Istanbul University-Cerrahpasa Faculty of Medicine, Istanbul, Turkey
Search for more papers by this authorEmine Zengin
Faculty of Medicine, Department of Pediatric Hematology, Kocaeli University, Kocaeli, Turkey
Search for more papers by this authorSema Aylan Gelen
Faculty of Medicine, Department of Pediatric Hematology, Kocaeli University, Kocaeli, Turkey
Search for more papers by this authorGul Nihal Ozdemir
Pediatric Hematology Division, Istanbul Kanuni Sultan Suleyman Education and Research Hospital, Istanbul, Turkey
Search for more papers by this authorYildiz Yildirmak
Pediatric Hematology Division, Ministry of Health Sisli Etfal Education and Research Hospital, Istanbul, Turkey
Search for more papers by this authorOmer Dogru
Pediatric Hematology and Oncology Department, Marmara University School of Medicine, Istanbul, Turkey
Search for more papers by this authorTurkan Tansel
Istanbul Medical Faculty, Department of Cardiovascular Surgery, Istanbul University, Istanbul, Turkey
Search for more papers by this authorKhusan Khodzhaev
Department of Genetics, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey
Institute of Health Sciences, Istanbul University, Istanbul, Turkey
Search for more papers by this authorOzlem Toluk
Department of Biostatistics and Medical Informatics, Bezmialem Vakif University Faculty of Medicine, Istanbul, Turkey
Search for more papers by this authorUgur Ozbek
Department of Genetics, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey
Faculty of Medicine, Department of Medical Genetics, Acibadem Mehmet Ali Aydinlar University, Istanbul, Turkey
Search for more papers by this authorCorresponding Author
Muge Sayitoglu
Department of Genetics, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey
Correspondence
Muge Sayitoglu, Department of Genetics, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Vakif Gureba Cad. 34093, Istanbul, Turkey.
Email: [email protected]
Search for more papers by this authorYucel Erbilgin
Department of Genetics, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey
Search for more papers by this authorOzden Hatirnaz Ng
Department of Genetics, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey
Faculty of Medicine, Department of Medical Biology, Acibadem Mehmet Ali Aydinlar University, Istanbul, Turkey
Search for more papers by this authorIsmail Can
Institute of Health Sciences, Istanbul University, Istanbul, Turkey
Search for more papers by this authorSinem Firtina
Institute of Health Sciences, Istanbul University, Istanbul, Turkey
Faculty of Art and Science, Department of Molecular Biology and Genetics, Istinye University, İstanbul, Turkey
Search for more papers by this authorFulya Kucukcankurt
Institute of Health Sciences, Istanbul University, Istanbul, Turkey
Faculty of Medicine, Altınbaş University, Istanbul, Turkey
Search for more papers by this authorSerap Karaman
Istanbul Faculty of Medicine, Pediatric Hematology Oncology Department, Istanbul University, Istanbul, Turkey
Search for more papers by this authorZeynep Karakas
Istanbul Faculty of Medicine, Pediatric Hematology Oncology Department, Istanbul University, Istanbul, Turkey
Search for more papers by this authorTulin Tiraje Celkan
Pediatric Hematology Oncology Department, Istanbul University-Cerrahpasa Faculty of Medicine, Istanbul, Turkey
Search for more papers by this authorEmine Zengin
Faculty of Medicine, Department of Pediatric Hematology, Kocaeli University, Kocaeli, Turkey
Search for more papers by this authorSema Aylan Gelen
Faculty of Medicine, Department of Pediatric Hematology, Kocaeli University, Kocaeli, Turkey
Search for more papers by this authorGul Nihal Ozdemir
Pediatric Hematology Division, Istanbul Kanuni Sultan Suleyman Education and Research Hospital, Istanbul, Turkey
Search for more papers by this authorYildiz Yildirmak
Pediatric Hematology Division, Ministry of Health Sisli Etfal Education and Research Hospital, Istanbul, Turkey
Search for more papers by this authorOmer Dogru
Pediatric Hematology and Oncology Department, Marmara University School of Medicine, Istanbul, Turkey
Search for more papers by this authorTurkan Tansel
Istanbul Medical Faculty, Department of Cardiovascular Surgery, Istanbul University, Istanbul, Turkey
Search for more papers by this authorKhusan Khodzhaev
Department of Genetics, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey
Institute of Health Sciences, Istanbul University, Istanbul, Turkey
Search for more papers by this authorOzlem Toluk
Department of Biostatistics and Medical Informatics, Bezmialem Vakif University Faculty of Medicine, Istanbul, Turkey
Search for more papers by this authorUgur Ozbek
Department of Genetics, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey
Faculty of Medicine, Department of Medical Genetics, Acibadem Mehmet Ali Aydinlar University, Istanbul, Turkey
Search for more papers by this authorCorresponding Author
Muge Sayitoglu
Department of Genetics, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey
Correspondence
Muge Sayitoglu, Department of Genetics, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Vakif Gureba Cad. 34093, Istanbul, Turkey.
Email: [email protected]
Search for more papers by this authorAbstract
Introduction
The lymphoid enhancer factor 1 (LEF1) is a DNA-binding transcription factor that functions in the Wnt signaling pathway. Increased LEF1 activity is associated with progression of several types of cancer including leukemia. Here, we investigated LEF1 isoform expression and genomic variations in acute lymphoblastic leukemia (ALL).
Methods
LEF1 isoform expression was evaluated by quantitative real-time PCR in 87 newly diagnosed childhood ALL patients and controls. Moreover, Western blot analysis was performed for detection of LEF1 expression and the hotspot region of LEF1 was screened by deep sequencing.
Results
The LEF1 mRNA expression of B cell ALL patients was higher than the controls (LEF1-total P = .011, LEF1-long P = .026). Moreover, B-ALL samples showing higher total LEF1 expression had significantly shorter relapse-free survival (P = .008) and overall survival (P = .011). Although full-length LEF1 expression was similar to the controls in T-ALL, 50% (n = 15) of the ALL patients had increased full-length LEF1 protein expression. Imbalance between short- and full-length LEF1 isoforms may lead to cell survival in ALL. Beside the LEF1 activation, LEF1 gene variations were rarely observed in our cohort.
Conclusion
The results indicate that the Wnt pathway may have a pathogenic function in a group of ALL patients and high LEF1-total expression might be a marker for shorter relapse-free survival time in B cell ALL.
CONFLICT OF INTEREST
The authors declare no competing financial interests.
Open Research
DATA AVAILABILITY STATEMENT
Data available in article supplementary material. The data that supports the findings of this study are available in the supplementary material of this article
Supporting Information
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ijlh13513-sup-0001-Supinfo.docxWord document, 5.6 MB | Supplementary Material |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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