Abstract
Objectives: Recently, hyperactivation of the Wnt signaling pathway has been implicated in leukomogenesis, so we studied the epigenetic dysfunction of SFRP1,2 and expression of interleukin2 receptor α chain (IL2Rα, also known as CD25) and its prognostic impact in acute myeloblastic leukemia (AML). Methods: We studied the methylation profile of SFRP1,2 in AML cells by methylation-specific polymerase chain reaction (MSP) and the hyper expression of IL2Rα (CD25) by flowcytometry. Results: We analyzed the methylation profile of SFRP1,2 in 40 de novo AML patients. The percentage of hypermethylation in the patient samples were 37.5% for SFRP1, 12.5% for SFRP2. CD25 was positive in 12(30%) of 40 patients AML. We found that in patients whom 60 years and younger with intermediate risk cytogenetics in de novo AML, hypermethylation of SFRP1 and CD25 were accompanied with relapse (P=0.024). Conclusion: Our data indicates that in a subgroup of AML patients, hypermethylation of SFRP1 and high expression of CD25 predict relapse
Highlights
Acute myeloid leukemia is a clonal hematopoietic disease associated by aberrant renewal of hematopoietic stem cells, differentiation arrest at blast cells, peripheral blood infiltration of blasts
This leads to b-catenin stabilization and its translocation into the nucleus where it binds to a number of transcription factors, like T-cell factor (TCF) and lymphoid enhancing factor-1 (LEF1) [10]
We aimed to study the prognostic impact of hypermethylated SFRP1,2 and overexpression of CD25 in acute myeloblastic leukemia (AML) patients
Summary
Acute myeloid leukemia is a clonal hematopoietic disease associated by aberrant renewal of hematopoietic stem cells, differentiation arrest at blast cells, peripheral blood infiltration of blasts. Attachment of Wnt to the Frizzled receptor leads to an inhibition of the GSK3b by the protein Dishevelled activation. This leads to b-catenin stabilization and its translocation into the nucleus where it binds to a number of transcription factors, like T-cell factor (TCF) and lymphoid enhancing factor-1 (LEF1) [10]. In a case of hypermethylation of SFRP genes, its inhibitory effect on wnt singnaling pathway was lost which leads to elevation of cytoplasmic and nuclear levels of β- cathenin and in turn β-cathenin as a transcription factor increases expression of cyclin D and Myc genes that are included in cell cycle regulation [12]. We aimed to study the prognostic impact of hypermethylated SFRP1,2 and overexpression of CD25 in AML patients
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