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EP300-ZNF384 fusion gene product up-regulates GATA3 gene expression and induces hematopoietic stem cell gene expression signature in B-cell precursor acute lymphoblastic leukemia cells.
Int J Hematol. 2017 Aug; 106(2):269-281.IJ

Abstract

ZNF384-related fusion genes are associated with a distinct subgroup of B-cell precursor acute lymphoblastic leukemias in childhood, with a frequency of approximately 3-4%. We previously identified a novel EP300-ZNF384 fusion gene. Patients with the ZNF384-related fusion gene exhibit a hematopoietic stem cell (HSC) gene expression signature and characteristic immunophenotype with negative or low expression of CD10 and aberrant expression of myeloid antigens, such as CD33 and CD13. However, the molecular basis of this pathogenesis remains completely unknown. In the present study, we examined the biological effects of EP300-ZNF384 expression induced by retrovirus-mediated gene transduction in an REH B-cell precursor acute lymphoblastic leukemia cell line, and observed the acquisition of the HSC gene expression signature and an up-regulation of GATA3 gene expression, as assessed by microarray analysis. In contrast, the gene expression profile induced by wild-type ZNF384 in REH cells was significantly different from that by EP300-ZNF384 expression. Together with the results of reporter assays, which revealed the enhancement of GATA3-promoter activity by EP300-ZNF384 expression, these findings suggest that EP300-ZNF384 mediates GATA3 gene expression and may be involved in the acquisition of the HSC gene expression signature and characteristic immunophenotype in B-cell precursor acute lymphoblastic leukemia cells.

Authors+Show Affiliations

Department of Pediatric Hematology and Oncology Research, National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan. Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine, 3-1-3 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.Department of Pediatric Hematology and Oncology Research, National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan. Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine, 3-1-3 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.Department of Pediatric Hematology and Oncology Research, National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan.Department of Pediatric Hematology and Oncology Research, National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan.Department of Pediatric Hematology and Oncology Research, National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan.Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine, 3-1-3 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.Department of Pediatrics and Adolescent Medicine, Juntendo University Graduate School of Medicine, 3-1-3 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.Department of Pediatric Hematology and Oncology Research, National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan.Department of Pediatrics, St. Luke's International Hospital, 9-1 Akashi-cho, Chuo-ku, Tokyo, 104-8560, Japan.Department of Pediatric Hematology and Oncology Research, National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo, 157-8535, Japan. kiyokawa-n@ncchd.go.jp.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28378055

Citation

Yaguchi, Akinori, et al. "EP300-ZNF384 Fusion Gene Product Up-regulates GATA3 Gene Expression and Induces Hematopoietic Stem Cell Gene Expression Signature in B-cell Precursor Acute Lymphoblastic Leukemia Cells." International Journal of Hematology, vol. 106, no. 2, 2017, pp. 269-281.
Yaguchi A, Ishibashi T, Terada K, et al. EP300-ZNF384 fusion gene product up-regulates GATA3 gene expression and induces hematopoietic stem cell gene expression signature in B-cell precursor acute lymphoblastic leukemia cells. Int J Hematol. 2017;106(2):269-281.
Yaguchi, A., Ishibashi, T., Terada, K., Ueno-Yokohata, H., Saito, Y., Fujimura, J., Shimizu, T., Ohki, K., Manabe, A., & Kiyokawa, N. (2017). EP300-ZNF384 fusion gene product up-regulates GATA3 gene expression and induces hematopoietic stem cell gene expression signature in B-cell precursor acute lymphoblastic leukemia cells. International Journal of Hematology, 106(2), 269-281. https://doi.org/10.1007/s12185-017-2220-6
Yaguchi A, et al. EP300-ZNF384 Fusion Gene Product Up-regulates GATA3 Gene Expression and Induces Hematopoietic Stem Cell Gene Expression Signature in B-cell Precursor Acute Lymphoblastic Leukemia Cells. Int J Hematol. 2017;106(2):269-281. PubMed PMID: 28378055.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - EP300-ZNF384 fusion gene product up-regulates GATA3 gene expression and induces hematopoietic stem cell gene expression signature in B-cell precursor acute lymphoblastic leukemia cells. AU - Yaguchi,Akinori, AU - Ishibashi,Takeshi, AU - Terada,Kazuki, AU - Ueno-Yokohata,Hitomi, AU - Saito,Yuya, AU - Fujimura,Junya, AU - Shimizu,Toshiaki, AU - Ohki,Kentaro, AU - Manabe,Atsushi, AU - Kiyokawa,Nobutaka, Y1 - 2017/04/04/ PY - 2016/11/04/received PY - 2017/03/21/accepted PY - 2017/03/20/revised PY - 2017/4/6/pubmed PY - 2017/10/6/medline PY - 2017/4/6/entrez KW - CD33 KW - EP300 KW - GATA3 KW - Transcription KW - ZNF384 SP - 269 EP - 281 JF - International journal of hematology JO - Int. J. Hematol. VL - 106 IS - 2 N2 - ZNF384-related fusion genes are associated with a distinct subgroup of B-cell precursor acute lymphoblastic leukemias in childhood, with a frequency of approximately 3-4%. We previously identified a novel EP300-ZNF384 fusion gene. Patients with the ZNF384-related fusion gene exhibit a hematopoietic stem cell (HSC) gene expression signature and characteristic immunophenotype with negative or low expression of CD10 and aberrant expression of myeloid antigens, such as CD33 and CD13. However, the molecular basis of this pathogenesis remains completely unknown. In the present study, we examined the biological effects of EP300-ZNF384 expression induced by retrovirus-mediated gene transduction in an REH B-cell precursor acute lymphoblastic leukemia cell line, and observed the acquisition of the HSC gene expression signature and an up-regulation of GATA3 gene expression, as assessed by microarray analysis. In contrast, the gene expression profile induced by wild-type ZNF384 in REH cells was significantly different from that by EP300-ZNF384 expression. Together with the results of reporter assays, which revealed the enhancement of GATA3-promoter activity by EP300-ZNF384 expression, these findings suggest that EP300-ZNF384 mediates GATA3 gene expression and may be involved in the acquisition of the HSC gene expression signature and characteristic immunophenotype in B-cell precursor acute lymphoblastic leukemia cells. SN - 1865-3774 UR - https://www.unboundmedicine.com/medline/citation/28378055/EP300_ZNF384_fusion_gene_product_up_regulates_GATA3_gene_expression_and_induces_hematopoietic_stem_cell_gene_expression_signature_in_B_cell_precursor_acute_lymphoblastic_leukemia_cells_ L2 - https://dx.doi.org/10.1007/s12185-017-2220-6 DB - PRIME DP - Unbound Medicine ER -