Yucel Erbilgin1, Ozden Hatirnaz Ng1,2, Ismail Can3, Sinem Firtina3,4, Fulya Kucukcankurt3,5, Serap Karaman6, Zeynep Karakas6, Tulin Tiraje Celkan7, Emine Zengin8, Sema Aylan Gelen8, Gul Nihal Ozdemir9, Yildiz Yildirmak10, Omer Dogru11, Turkan Tansel12, Khusan Khodzhaev1,3, Ozlem Toluk13, Ugur Ozbek1,14, Muge Sayitoglu1. 1. Department of Genetics, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey. 2. Faculty of Medicine, Department of Medical Biology, Acibadem Mehmet Ali Aydinlar University, Istanbul, Turkey. 3. Institute of Health Sciences, Istanbul University, Istanbul, Turkey. 4. Faculty of Art and Science, Department of Molecular Biology and Genetics, Istinye University, İstanbul, Turkey. 5. Faculty of Medicine, Altınbaş University, Istanbul, Turkey. 6. Istanbul Faculty of Medicine, Pediatric Hematology Oncology Department, Istanbul University, Istanbul, Turkey. 7. Pediatric Hematology Oncology Department, Istanbul University-Cerrahpasa Faculty of Medicine, Istanbul, Turkey. 8. Faculty of Medicine, Department of Pediatric Hematology, Kocaeli University, Kocaeli, Turkey. 9. Pediatric Hematology Division, Istanbul Kanuni Sultan Suleyman Education and Research Hospital, Istanbul, Turkey. 10. Pediatric Hematology Division, Ministry of Health Sisli Etfal Education and Research Hospital, Istanbul, Turkey. 11. Pediatric Hematology and Oncology Department, Marmara University School of Medicine, Istanbul, Turkey. 12. Istanbul Medical Faculty, Department of Cardiovascular Surgery, Istanbul University, Istanbul, Turkey. 13. Department of Biostatistics and Medical Informatics, Bezmialem Vakif University Faculty of Medicine, Istanbul, Turkey. 14. Faculty of Medicine, Department of Medical Genetics, Acibadem Mehmet Ali Aydinlar University, Istanbul, Turkey.
Abstract
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.
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.
Authors: Tiffany Carr; Stephanie McGregor; Sheila Dias; Mihalis Verykokakis; Michelle M Le Beau; Hai-Hui Xue; Mikael Sigvardsson; Elizabeth T Bartom; Barbara L Kee Journal: Front Immunol Date: 2022-03-18 Impact factor: 7.561