Sinem FIRTINA, Özden HATIRNAZ NG, Yücel ERBİLGİN, İbrahim Celaleddin HAZNEDAROĞLU, Müge SAYİTOĞLU

Yetişkin Lenfoid ve Miyeloid Malignitelerde LEF1 İzoformlarının Farklı Ekspresyonu

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..

Anahtar Kelimeler:

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

Differential Expression of LEF1 Isoforms in Adult Lymphoid and Myeloid Malignancies

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,

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