Volume 43, Issue 5 pp. 1093-1103
ORIGINAL ARTICLE

Prognostic evidence of LEF1 isoforms in childhood acute lymphoblastic leukemia

Yucel Erbilgin

Yucel Erbilgin

Department of Genetics, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey

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Ozden Hatirnaz Ng

Ozden 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

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Ismail Can

Ismail Can

Institute of Health Sciences, Istanbul University, Istanbul, Turkey

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Sinem Firtina

Sinem Firtina

Institute of Health Sciences, Istanbul University, Istanbul, Turkey

Faculty of Art and Science, Department of Molecular Biology and Genetics, Istinye University, İstanbul, Turkey

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Fulya Kucukcankurt

Fulya Kucukcankurt

Institute of Health Sciences, Istanbul University, Istanbul, Turkey

Faculty of Medicine, Altınbaş University, Istanbul, Turkey

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Serap Karaman

Serap Karaman

Istanbul Faculty of Medicine, Pediatric Hematology Oncology Department, Istanbul University, Istanbul, Turkey

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Zeynep Karakas

Zeynep Karakas

Istanbul Faculty of Medicine, Pediatric Hematology Oncology Department, Istanbul University, Istanbul, Turkey

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Tulin Tiraje Celkan

Tulin Tiraje Celkan

Pediatric Hematology Oncology Department, Istanbul University-Cerrahpasa Faculty of Medicine, Istanbul, Turkey

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Emine Zengin

Emine Zengin

Faculty of Medicine, Department of Pediatric Hematology, Kocaeli University, Kocaeli, Turkey

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Sema Aylan Gelen

Sema Aylan Gelen

Faculty of Medicine, Department of Pediatric Hematology, Kocaeli University, Kocaeli, Turkey

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Gul Nihal Ozdemir

Gul Nihal Ozdemir

Pediatric Hematology Division, Istanbul Kanuni Sultan Suleyman Education and Research Hospital, Istanbul, Turkey

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Yildiz Yildirmak

Yildiz Yildirmak

Pediatric Hematology Division, Ministry of Health Sisli Etfal Education and Research Hospital, Istanbul, Turkey

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Omer Dogru

Omer Dogru

Pediatric Hematology and Oncology Department, Marmara University School of Medicine, Istanbul, Turkey

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Turkan Tansel

Turkan Tansel

Istanbul Medical Faculty, Department of Cardiovascular Surgery, Istanbul University, Istanbul, Turkey

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Khusan Khodzhaev

Khusan Khodzhaev

Department of Genetics, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey

Institute of Health Sciences, Istanbul University, Istanbul, Turkey

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Ozlem Toluk

Ozlem Toluk

Department of Biostatistics and Medical Informatics, Bezmialem Vakif University Faculty of Medicine, Istanbul, Turkey

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Ugur Ozbek

Ugur 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

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Muge Sayitoglu

Corresponding 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]

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First published: 12 April 2021
Citations: 2

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.

CONFLICT OF INTEREST

The authors declare no competing financial interests.

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

The full text of this article hosted at iucr.org is unavailable due to technical difficulties.