Transcriptional upregulation of p21/WAF/Cip1 in myeloid leukemic blasts expressing AML1-ETO

被引：24

作者：

Berg, Tobias

Fliegauf, Manfred ^{[2
]}

Burger, Jan ^{[3
]}

Staege, Martin S. ^{[4
]}

Liu, Shaohua ^{[5
]}

Martinez, Natalia ^{[6
]}

Heidenreich, Olaf ^{[7
]}

Burdach, Stefan ^{[8
,9
]}

Haferlach, Torsten ^{[10
]}

Werner, Milton H. ^{[11
]}

Luebbert, Michael ^{[1
]}

机构：

[1] Univ Freiburg, Med Ctr, Dept Med, Div Hematol Oncol, D-79106 Freiburg, Germany

[2] Univ Freiburg, Med Ctr, Dept Pediat, D-79106 Freiburg, Germany

[3] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA

[4] Univ Halle Wittenberg, Div Pediat Hematol Oncol, Halle, Germany

[5] Rockefeller Univ, Lab Mol Biophys, New York, NY 10021 USA

[6] Univ Tubingen, Inst Cell Biol, Dept Mol Biol, Tubingen, Germany

[7] Newcastle Univ, No Inst Canc Res, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England

[8] Tech Univ Munich, Pediat Oncol Ctr, Munich, Germany

[9] Tech Univ Munich, Dept Pediat, Munich, Germany

[10] MLL Munich Leukemia Lab, Munich, Germany

[11] Celtaxsys, ATDC Biosci Ctr, Atlanta, GA USA

来源：

HAEMATOLOGICA-THE HEMATOLOGY JOURNAL | 2008年 / 93卷 / 11期

关键词：

cell cycle; acute myeloid leukemia; chromosomal translocation;

D O I：

10.3324/haematol.13044

中图分类号：

R5 [内科学];

学科分类号：

1002 [临床医学]; 100201 [内科学];

摘要：

An inducible model for conditional expression of AML1-ETO in myeloid U-937 cells was generated previously to determine cellular effects of AML1-ETO and to identify target genes. Induction of AML1-ETO expression in U-937 resulted in reduced cell growth, G1 arrest and apoptosis. Microarray analysis showed more genes up-regulated than down-regulated (180 vs. 69). Clustering of AML1-ETO-positive and -negative cell lines was possible based on these differentially expressed genes. p21/WAF/Cip1 (CDKN1A) was up-regulated 4.6-fold upon induction of AML1-ETO which was confirmed in additional experiments. Knock-down of AML1-ETO by siRNA could reduce p21/WAF/Cip1 expression in Kasumi-1 cells. mRNA expression analysis of p21/WAF/Cip1 in a large cohort of acute myeloid leukemia patients demonstrated a significantly higher expression in AML1-ETO-positive leukemia. The increased expression of p21/WAF/Cip1 in primary leukemic blasts suggests that elevated p21/WAF/Cip1 levels may contribute to specific features observed in AML1-ETO positive leukemia.

引用

页码：1728 / 1733

页数：6

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