KRONİK MİYELOİD LÖSEMİLİ HASTALARDA ERKEN MOLEKÜLER YANIT TAHMİNİ İÇİN PRSS57 GEN İFADESİ

Abstract

Amaç: Kronik myeloid lösemide (KML) tirozin kinaz inhibitörlerine verilen yanıtın moleküler takibi BCR/ABL transkriptlerine göre yapılmaktadır. Tedavi başlangıcından sonra hastalar üç aylık periyotlarla moleküler analizlerle takip edilmektedir. Tedavi sonrası üç aylık takipte BCR/ABL Uluslararası değeri (IS) %10 ve altına düştüğünde erken moleküler yanıt (EMY) başarılı kabul edilmektedir. KML hastalarında önemli prognostik değeri olduğu bildirilen bu yanıtın uzun vadede olumlu sonuçlarla ilişkili olduğu bulunmuştur. Ancak EMY başarısız olan hastalar için hastalığın ilerlemesi ve tedavi yönetimi için üç aylık takip geç olabilmektedir. Bu nedenle tanı sırasında prognozun tahmini sağlayabilecek ek biomarkerlara ihtiyaç duyulmaktadır. Gereç ve Yöntemler: Çalışmamızda serin proteaz 57 (PRSS57) gen ifadesinin EMY ile ilişkisi araştırıldı. 20 KML hastasında PRSS57 gen ifadesi kantitatif ters transkriptaz polimeraz zincir reaksiyonu (qRT-PZR) yöntemiyle belirlendi ve EMY ile ilişkisi analiz edildi. Bulgular: PRSS57 gen ifadesi EMY başarısız hastalarda anlamlı derecede yüksek olduğu (p=0,002) ve BCR/ABL IS değeri ile pozitif yönde bağlantılı olduğu bulundu. Sonuçlarımız aynı zamanda PRSS gen ifadesinin tedavi sonrası izlem örneklerinde azaldığını gösterdi. Sonuç: Bu bulgular tanıda PRSS57 ifadesinin EMY başarısızlığı riski yüksek hastaların tahmininde yararlı olabileceğini göstermektedir.

Keywords

• KML
• erken moleküler yanıt
• PRSS57

PRSS57 GENE EXPRESSION PREDICTS EARLY MOLECULAR RESPONSE FAILURE IN PATIENTS WITH CHRONIC MYELOID LEUKEMIA

Abstract

Objectives: The molecular response to tyrosine kinase inhibitors in chronic myeloid leukemia (CML) is monitored by quantitative detection of BCR/ABL transcripts. After the initiation of the treatment, patients are followed-up with molecular analysis at three-month intervals. Early molecular response (EMR) is considered achieved when the BCR/ABL international scale (IS) is 10% or below in the three-month follow-up after treatment. This response, which has been reported to have a strong prognostic significance in CML patients, is associated with favorable longterm outcomes. However, the three-month follow-up period may be too long in terms of disease progression and treatment management for patients who fail to achieve EMR. Therefore, additional biomarkers that can predict the prognosis are needed. Material and Methods: This study investigated the relationship between serine protease 57 (PRSS57) gene expression, and EMR. The PRSS57 gene expression in 20 CML patients was determined by the quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) method and its relationship with EMR was analyzed. Results: The PRSS57 gene expression was found to be significantly higher in patients who failed EMR (p=0.002) and positively correlated with BCR/ ABL IS value (r=0.567, p=0.009). Our results also revealed that the PRSS57 gene expression was decreased in the post-treatment follow-up sample when compared with the diagnostic sample (p=0.000). Conclusion: These findings indicate that the PRSS57 gene expression in diagnosis may be useful for predicting patients at high risk of EMR failure.

Keywords

• CML
• early molecular response
• PRSS57

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