Evaluation of secreted frizzled-related protein-4 methylation profiles in patients with BCR/ABL positive chronic myeloid leukemia

• Published in: World cancer research journal Vol. 8
• Main Authors: M. Pehlivan, N. Sirin, G. Hayri Ozsan, Z. Yuce, H. Ogun Sercan
• Format: Journal Article
• Language: English
• Published: Verduci Editore 01-01-2021
• Subjects: cml; cytogenetics; dna methylation; sfrp4; wnt signaling
• ISSN: 2372-3416
• DOI: 10.32113/wcrj_20215_1967

Objective: Chronic Myeloid Leukemia (CML) is a myeloproliferative disorder characterized by the chromosomal translocation t(9;22) encoding for the Bcr/Abl fusion gene. Secreted Frizzled Related Protein (sFRP) gene products are antagonists of Wnt signaling and their epigenetic silencing has been reported in different types of leukemia. While epigenetic silencing has been extensively reported for sFRP, sFRP4 is a family member less studied. We aimed to study epigenetic silencing of sFRP4 in CML patients. Patients and Methods: Epigenetics alterations in the promoter region of the sFRP4 gene were analyzed in 43 CML patients. DNA methylation of CpGs in the sFRP4 promotor region was investigated using methylation specific PCR. Conventional cytogenetic analyzes were performed directly and after 24 h short cultures from bone marrow samples of patients with a preliminary diagnosis of CML. Results: 42 out of the 43 CML patients investigated were shown to be unmethylated at the sFRP4 promoter region, while in 1 patient hemimethylation was observed. This patient was the only one in which cytogenetic progression with additional chromosomal abnormalities were identified. All others achieved major or complete cytogenetic remission. Conclusions: We observed that sFRP4 methylation is a very rare CML patients’ phenomenon. Yet when observed it may implicate disease progression and therapy resistance. A large study needs to clarify the implication of methylated sFRP4 in CML progression.