title: WNT5A expression is regulated by the status of its promoter methylation in leukaemia and can inhibit leukemic cell malignant proliferation.
abstract: Although down-regulation of WNT5A expression has been reported in some types of leukaemias, the level of WNT5A expression has not been assessed in leukaemia complete remission (CR) cases, the relationship among WNT5A expression level, the status of its promoter methylation, and the curative effect of leukaemia has not been reported, and the effect of WNT5A on cell proliferation has not been assessed. In this study, we analyzed WNT5A expression in various kinds of leukaemia cases, leukaemia CR cases, non-malignant hematopoietic (NMH) cases, as well as in leukemic cell lines and CD34+ cells. The methylation status of the WNT5A promoter and the levels of the Wnt5a protein were also studied. We also investigated the effect of Wnt5a on leukemic cell proliferation. WNT5A expression level was higher in NMH but lower in leukaemia cases compared to that in CR-cases (P<0.01), and was expressed at low level in leukemic cell lines K562, U937 and Jurkat. Wnt5a protein was positive in NMH, CR cases and CD34+, but negative in leukaemia cases. WNT5A promoter was methylated in leukaemia cases and all leukemic cell lines, but not in NMH and CR cases. WNT5A expression was up-regulated after exposure to the demethylating agent 5-Aza-2'-deoxycytidine (Aza) in the K562, U937, Jurkat leukemic cell lines and in 83.3% (10/12) of CR patients after cure, respectively. The increased Wnt5a protein can inhibit K562 malignant proliferation and arrest cell cycle at the G2/M phase after exposure to Aza. These results indicate that WNT5A expression was restored in complete remission cases due to demethylation, and Wnt5a can inhibit leukaemic cell proliferation. We propose that WNT5A can act as a suppressor factor in leukemogenesis and can be used as a potential marker for curative effect assessment in leukaemia.
authors.affiliation: Department of Clinical Hematology, Third Military Medical University, Chongqing 400038, PR China.
authors.forename: Gang
authors.initials: G
authors.lastname: Deng
authors.forename: Zhao Quan
authors.initials: ZQ
authors.lastname: Li
authors.forename: Chen
authors.initials: C
authors.lastname: Zhao
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yuan
authors.forename: Chang Chun
authors.initials: CC
authors.lastname: Niu
authors.forename: Chen
authors.initials: C
authors.lastname: Zhao
authors.forename: Jing
authors.initials: J
authors.lastname: Pan
authors.forename: Wei Ke
authors.initials: WK
authors.lastname: Si
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D049109:Cell Proliferation; D002648:Child; D019175:DNA Methylation / Q000502:physiology*; D015536:Down-Regulation; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D019169:Jurkat Cells; D020014:K562 Cells; D007938:Leukemia / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D014407:Tumor Cells, Cultured; D020298:U937 Cells; D051153:Wnt Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D000071818:Wnt-5a Protein; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D011518:Proto-Oncogene Proteins; C085389:WNT5A protein, human; D051153:Wnt Proteins; D000071818:Wnt-5a Protein