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

Year 2024, Volume: 7 Issue: 1, 32 - 36, 15.02.2024

Elif Nur Bozdağ Güven Çetin Serap Karaman Ayşegül Ünüvar Zeynep Karakaş Neslihan Abacı Sema Sırma Ekmekci

https://doi.org/10.26650/JARHS2024-1311348

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

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

Supporting Institution

Destekleyen kurum bulunmamaktadır.

References

• Surveillance, Epidemiology, and End Results (SEER) Program (www.seer.cancer.gov) SEER*Stat Database: Incidence - SEER Research Data, 8 Registries, Nov 2021 Sub (1975-2019) - Linked To County Attributes - Time Dependent (1990-2019) Income/ Rurality, 1969-2020 Counties, National Cancer Institute, DCCPS, Surveillance Research Program, released April 2022, based on the November 2021 submission. google scholar
• Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA Cancer J Clin 2022;72(1):7-33. google scholar
• O’Dwyer M. Multifaceted approach to the treatment of bcr-abl-positive leukemias. Oncologist 2002;7 Suppl 1:30-8. google scholar
• Hochhaus A, Baccarani M, Silver RT, Schiffer C, Apperley JF, Cervantes F, et al. European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia. Leukemia 2020;34(4):966-84. google scholar
• National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology Chronic Myeloid Leukemia (Version 1.2023). Retrieved from https://www.nccn.org/professionals/ physician_gls/pdf/cml.pdf google scholar
• Hehlmann R. The New ELN Recommendations for Treating CML. J Clin Med 2020;9(11):3671. google scholar
• Deininger MW, Shah NP, Altman JK, Berman E, Bhatia R, Bhatnagar B, et al. Chronic Myeloid Leukemia, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 2020;18(10):1385-415. google scholar
• Narlı Özdemir Z, Kılıçaslan NA, Yılmaz M, Eşkazan AE. Guidelines for the treatment of chronic myeloid leukemia from the NCCN and ELN: differences and similarities. Int J Hematol 2023;117(1):3-15. google scholar
• Hughes TP, Kaeda J, Branford S, Rudzki Z, Hochhaus A, Hensley ML, et al. Frequency of major molecular responses to imatinib or interferon alfa plus cytarabine in newly diagnosed chronic myeloid leukemia. N Engl J Med 2003;349(15):1423-32. google scholar
• Hughes T, Deininger M, Hochhaus A, Branford S, Radich J, Kaeda J, et al. Monitoring CML patients responding to treatment with tyrosine kinase inhibitors: review and recommendations for harmonizing current methodology for detecting BCR-ABL transcripts and kinase domain mutations and for expressing results. Blood 2006;108(1):28-37. google scholar
• Jabbour E, Cortes JE, Kantarjian HM. Molecular monitoring in chronic myeloid leukemia: response to tyrosine kinase inhibitors and prognostic implications. Cancer 2008;112(10):2112-8. google scholar
• Bhamidipati PK, Kantarjian H, Cortes J, Cornelison AM, Jabbour E. Management of imatinib-resistant patients with chronic myeloid leukemia. Ther Adv Hematol 2013;4(2):103-17. google scholar
• Cross NC, White HE, Müller MC, Saglio G, Hochhaus A. Standardized definitions of molecular response in chronic myeloid leukemia. Leukemia 2012;26(10):2172-5. google scholar
• Harada I, Sasaki H, Murakami K, Nishiyama A, Nakabayashi J, Ichino M, et al. Compromised anti-tumor-immune features of myeloid cell components in chronic myeloid leukemia patients. Sci Rep 2021;11(1):18046. google scholar
• Kok CH, Yeung DT, Lu L, Watkins DB, Leclercq TM, Dang P, et al. Gene expression signature that predicts early molecular response failure in chronic-phase CML patients on frontline imatinib. Blood Adv 2019;3(10):1610-21. google scholar
• Hughes TP, Saglio G, Kantarjian HM, Guilhot F, Niederwieser D, Rosti G,et al. Early molecular response predicts outcomes in patients with chronic myeloid leukemia in chronic phase treated with frontline nilotinib or imatinib. Blood 2014;123(9):1353-60. google scholar
• Baccarani M, Cortes J, Pane F, Niederwieser D, Saglio G, Apperley J, et al. Chronic myeloid leukemia: an update of concepts and management recommendations of European LeukemiaNet. J Clin Oncol 2009;27(35):6041-51. google scholar