Differential Expression of LEF1 Isoforms in Adult Lymphoid and Myeloid Malignancies

Year 2021, Volume: 11 Issue: 3, 184 - 188, 08.12.2021

Sinem Fırtına , Özden Hatırnaz Ng , Yücel Erbilgin , İbrahim Celaleddin Haznedaroğlu , Müge Sayitoğlu

https://doi.org/10.26650/experimed.2021.993743

Abstract

Objective: Lymphoid enhancer-binding factor-1 (LEF1) is one of the key regulators of lymphocyte proliferation and its aberrant ex-pression is a prognostic factor for lymphoid or myeloid malignancies. In this study, we focused on the expression of LEF1 isoforms in several hematological malignancies and found tissuespecific dif-ferential expression for the full-length (FL)-LEF1 gene and its tumor suppressor (∆LEF1) variant.

Material and Method: Fifty-three leukemia/lymphoma patients were included in this study. Diagnostic samples of “lymphoid group” patients: Chronic Lymphoblastic Leukemia (CLL) (n=10), B-cell Acute Lymphoblastic Leukemia (B-ALL) (n=9) and “myeloid group” patients: Chronic Myeloblastic Leukemia (CML) (n=12), Acute Myeloid Leukemia (AML) (n=13), and Multiple Myeloma (MM) (n=9) were studied. Healthy bone marrow, peripheral blood cells, and CD34 positive cells were used as controls. Total (T) and FL-LEF1 transcript levels were examined by using quantitative real-time polymerase chain reaction (qRT-PCR). T and FL-LEF1 mRNA ratios were also evaluated for calculation of ∆LEF1.

Results:LEF1 levels were significantly high in lymphoid malignan-cies, but MM and AML patients have decreased LEF1 levels. Al-though CLL patients have high FL-LEF1 levels, the ratio of the T/FL levels was significantly decreased.

Conclusion:LEF1 is a proliferation factor for lymphocytes and not only its differential overexpression but also the ratio of T/FL isoforms seem to accompany leukemia progress.

Keywords

LEF1, alternative splicing, lymphoid, myeloid, leukemia

Supporting Institution

TUBITAK

Project Number

106S112

Thanks

This work was supported and the Scientific and Technological Research Council of Turkey (TÜBİTAK, Project Nos. 106S112). We would like to thank to Suzin Catal Tatonyan for the support of laboratory studies.

Yetişkin Lenfoid ve Miyeloid Malignitelerde LEF1 İzoformlarının Farklı Ekspresyonu

Abstract

Amaç: Lenfositlerin çoğalmasındaki önemli düzenleyicilerden biri olan lenfoid güçlendirici bağlama faktörü-1 (LEF1)’in anormal eks-presyonu, lenfoid veya miyeloid maligniteler için prognostik bir fak-tördür. Bu çalışmada, farklı LEF1 izoformlarının çeşitli hematolojik malignitelerdeki ekspresyonu incelenmiş ve tüm uzunluktaki LEF1(FL-LEF1) anlatımı ile tümör baskılayıcı özelliğe sahip kısa izoformu (∆LEF1) için dokuya özgü farklılıklar tespit edilmiştir.

Gereç ve Yöntem: Çalışmaya 53 yetişkin lösemi/lenfoma hastasının tanı anı örnekleri dahil edilmiştir. Çalışmaya dahil edilen hastalar, “lenfoid grubu”; Kronik Lenfoblastik Lösemi (KLL) (n=10), B hücreli Akut Lenfoblastik Lösemi (B-ALL) (n=9) ve “miyeloid grubu”; Kronik Miyeloblastik Lösemi (KML) (n=12), Akut Miyeloid Lösemi (AML) (n=13) ve Multipl Miyelom (MM) (n=9) gruplarından oluşmaktadır. Sağlıklı kemik iliği, periferik kan hücreleri ve CD34 pozitif hücreler kontrol olarak kullanılmıştır. Total (T) ve FL-LEF1 transkript seviyeleri, gerçek zamanlı kantitatif polimeraz zincir reaksiyonu (qRT-PZR) ile incelenmiştir. T ve FL-LEF1 oranları da ∆LEF1 hesaplaması için değerlendirilmiştir.

Bulgular:LEF1'in lenfoid malignitelerde anlamlı derecede yüksek olduğu, MM ve AML hastalarında ise LEF1 seviyelerinde azalma olduğu görülmüştür. KLL hastalarında FL-LEF1 seviyeleri yüksek olma-sına rağmen, T/FL-LEF1 seviyelerinin önemli ölçüde azaldığı tespit edilmiştir.

Sonuç:LEF1, lenfositler için bir çoğalma faktörüdür ve sadece aşırı ekspresyonu değil, aynı zamanda T/FL-LEF1 izoformlarının oranının da lösemi ilerlemesine eşlik ettiğini düşündürmektedir..

Keywords

LEF1, alternatif kırpılma, lenfoid, miyeloid, lö-semi

Project Number

106S112

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