DNA Methyltransferase 1 Drives Transcriptional Down‐Modulation of β Catenin Antagonist Chibby1 Associated With the BCR‐ABL1 Gene of Chronic Myeloid Leukemia. Issue 4 (April 2015)

• Record Type: Journal Article
• Authors: Leo, Elisa; Mancini, Manuela; Castagnetti, Fausto; Gugliotta, Gabriele; Santucci, Maria Alessandra; Martinelli, Giovanni
• Is Part Of: Journal of cellular biochemistry. Volume 116:Issue 4(2015:Apr.)
• Page Start: 589
• Page End: 597
• Publication Date: 2015-04
• Subjects: Cytochemistry -- Periodicals; 572
• DOI: 10.1002/jcb.25010
• Languages: English
• ISSNs: 0730-2312

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>ABSTRACT</title> <sec id="jcb25010-sec-0001" sec-type="section"> <p>The decrease of Chibby1 (CBY1) contributes to β catenin constitutive activation associated with the presence of the <italic>BCR‐ABL1</italic> fusion gene of chronic myeloid leukemia (CML). This is mediated by transcriptional events and driven by DNA hyper‐methylation at promoter‐associated CpG islands of the CBY1‐encoding gene <italic>C22orf2</italic>. Moreover, CBY1 transcriptional induction proceeding from promoter de‐methylation is a component of <italic>BCR‐ABL1</italic>+ cell response to Imatinib (IM). Our study showed that DNA methyltransferase 1 (DNMT1) has a central role in the hyper‐methylation at the <italic>C22orf2</italic> promoter. Further investigation in leukemic hematopoietic progenitors from IM‐responsive and IM‐resistant CML patients at diagnosis failed to demonstrate any correlation between DNMT1‐driven hyper‐methylation of the <italic>C22orf2</italic> promoter and response to IM. Notably, the response to IM was neither predicted by DNMT1‐driven hyper‐methylation of <italic>BCL2‐like11</italic> at diagnosis. In conclusion, the hypermethylation of <italic>C22orf2</italic> and <italic>BCL2‐like11 promoters</italic> proceeding from DNMT1 is a crucial component of their reduced expression, but it is not directly involved in CML resistance to IM. It might rather contribute to the disease evolution towards a drug‐resistant phenotype in more advanced phases or blast crisis. J. Cell. Biochem. 116: 589–597, 2015. © 2014 Wiley Periodicals, Inc.</p> </sec> </abstract>