sFRP1 promoter methylation is associated with persistent Philadelphia chromosome in chronic myeloid leukemia

Leukemia Research
Melek PehlivanHakki Ogun Sercan

Abstract

Epigenetic silencing of sFRP genes has been shown to lead to constitutive activation of the canonical Wnt-signaling pathway. The first description of deregulated Wnt-signaling activation in a hematological malignancy was reported in chronic myeloid leukemia (CML). To investigate whether epigenetic silencing of sFRP is responsible for the observed Wnt activation in CML, we studied the methylation and mutational status of the sFRP1 promoter in 48 chronic phase CML patients. Of the 48 CML patients 41 were shown to be unmethylated, 6 patients hemi-methylated and 1 patient fully methylated at the sFRP1 promoter. Albeit observed infrequently in chronic phase CML, sFRP1 promoter methylation correlated with primary cytogenetic resistance to imatinib mesylate. sFRP1 promoter methylation may indicate a genetically more unstable form of disease resistant to therapy and provide a key biological difference in therapy resistant patients, in addition to a possible mechanism for the observed activation of canonical Wnt signaling in CML.

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Citations

Sep 12, 2012·Journal of Neuropathology and Experimental Neurology·Elisa Pérez-MagánBárbara Meléndez
Apr 2, 2013·Hematology·Sandhya AnnamaneniMohan Reddy Battini
Jul 31, 2012·Biochemical and Biophysical Research Communications·Li LiuYingmin Liang
Sep 8, 2016·APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica·Dora FabijanovicSemir Vranic
May 5, 2017·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Melek PehlivanHakkı Ogun Sercan
May 10, 2017·Experimental Hematology·Yong-Mi KimMichael Kahn
Feb 23, 2020·Cancers·Rashidah BaharudinNurul Syakima Ab Mutalib
Oct 24, 2017·Journal of Huazhong University of Science and Technology. Medical Sciences = Hua Zhong Ke Ji Da Xue Xue Bao. Yi Xue Ying De Wen Ban = Huazhong Keji Daxue Xuebao. Yixue Yingdewen Ban·Jie-Ke CuiZhao-Dong Zhong
Mar 18, 2019·Biochemistry. Biokhimii︠a︡·T I FetisovG A Belitsky
Nov 1, 2020·International Journal of Molecular Sciences·Monica Sharma, Kevin Pruitt

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