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

Tobias Berg; Manfred Fliegauf; Jan Burger; Martin S. Staege; Shaohua Liu; Natalia Martinez; Olaf Heidenreich; Stefan Burdach; Torsten Haferlach; Milton H. Werner; Michael Lübbert

doi:10.3324/haematol.13044

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

Tobias Berg, Manfred Fliegauf, Jan Burger, Martin S. Staege, Shaohua Liu, Natalia Martinez, Olaf Heidenreich, Stefan Burdach, Torsten Haferlach, Milton H. Werner, Michael Lübbert

Medicine and Health

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Abstract

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.

Original language	English
Pages (from-to)	1728-1733
Number of pages	6
Journal	Haematologica
Volume	93
Issue number	11
DOIs	https://doi.org/10.3324/haematol.13044
State	Published - Nov 2008

Keywords

Acute myeloid leukemia
Cell cycle
Chromosomal translocation

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title = "Transcriptional upregulation of p21/WAF/Cip1 in myeloid leukemic blasts expressing AML1-ETO",

abstract = "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.",

keywords = "Acute myeloid leukemia, Cell cycle, Chromosomal translocation",

author = "Tobias Berg and Manfred Fliegauf and Jan Burger and Staege, {Martin S.} and Shaohua Liu and Natalia Martinez and Olaf Heidenreich and Stefan Burdach and Torsten Haferlach and Werner, {Milton H.} and Michael L{\"u}bbert",

year = "2008",

month = nov,

doi = "10.3324/haematol.13044",

language = "English",

volume = "93",

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T1 - Transcriptional upregulation of p21/WAF/Cip1 in myeloid leukemic blasts expressing AML1-ETO

AU - Berg, Tobias

AU - Fliegauf, Manfred

AU - Burger, Jan

AU - Staege, Martin S.

AU - Liu, Shaohua

AU - Martinez, Natalia

AU - Heidenreich, Olaf

AU - Burdach, Stefan

AU - Haferlach, Torsten

AU - Werner, Milton H.

AU - Lübbert, Michael

PY - 2008/11

Y1 - 2008/11

N2 - 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.

AB - 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.

KW - Acute myeloid leukemia

KW - Cell cycle

KW - Chromosomal translocation

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

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