SUZ12 is a candidate target of the non-canonical WNT pathway in the progression of chronic myeloid leukemia.
Posted by rob on February 25, 2010 under Uncategorized | 
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SUZ12 is a candidate target of the non-canonical WNT pathway in the progression of chronic myeloid leukemia.
Genes Chromosomes Cancer. 2010 Feb;49(2):107-18
Authors: Pizzatti L, Binato R, Cofre J, Gomes BE, Dobbin J, Haussmann ME, D’Azambuja D, Bouzas LF, Abdelhay E
Polycomb proteins form multiprotein complexes that repress target genes by chromatin remodeling. In this work, we report that the SUZ12 polycomb gene is over-expressed in bone marrow samples of patients at the blastic phase of chronic myeloid leukemia. We also found a direct interaction between polycomb group genes and the WNT signaling pathway in chronic myeloid leukemia transformation. Electrophoretic mobility shift assay (EMSA), Chromatin immunoprecipitation assay (ChIP), and mass spectrometry assays identified noncanonical WNT pathway members, such as WNT5A and WNT11, bound to the SUZ12 promoter. Immunohistochemistry and immunofluorescence with WNT5A and WNT11 antibodies confirmed nuclear localization. Knockdown of WNTs 1, 5A, and 11 with RNAi approaches showed that WNT members are capable of activating SUZ12 transcription with varying promoter affinities. Finally, we suggest that SUZ12 is blocking cellular differentiation, as SUZ12 knockdown release differentiation programs in chronic myeloid blastic phase (CML-BP) transformed cell line.
PMID: 19847889 [PubMed - indexed for MEDLINE]