C/EBPα and C/EBPε induce the monocytic differentiation of myelomonocytic cells with the MLL-chimeric fusion gene

H. Matsushita, H. Nakajima, Y. Nakamura, H. Tsukamoto, Y. Tanaka, G. Jin, M. Yabe, S. Asai, R. Ono, T. Nosaka, K. Sugita, A. Morimoto, Y. Hayashi, T. Hotta, K. Ando, H. Miyachi

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

CCAAT/enhancer binding proteins (C/EBPs) have an important function in granulocytic differentiation, and are also involved in the leukemogenesis of acute myeloid leukemia (AML). Their involvement in myelomonocytic leukemia, however, is still unclear. Therefore, the expression and function of C/EBPs in myelomonocytic cells with MLL-fusion genes were investigated. Retinoic acid (RA) induced monocytic differentiation in the myelomonocytic cell lines with MLL-fusion genes, THP-1, MOLM-14 and HF-6 cells, accompanied by monocytic differentiation with the upregulation of C/EBPα and C/EBPε. Monocytic differentiation by RA treatment was confirmed in primary AML cells using a clonogenic assay. When the activity of C/EBPα or C/EBPε was introduced into HF-6 cells, their cellular growth was arrested through differentiation into monocytes with the concomitant marked downregulation of Myc. Cebpe mRNA was upregulated by the induction of C/EBPα-ER, but not vice versa, thus suggesting that C/EBPε may have an important function in the differentiation process. Introduction of Myc isoforms into HF-6 cells partially antagonized the C/EBPs effects. These findings suggest that the ectopic expression of C/EBPε, as well as C/EBPα, can induce the monocytic differentiation of myelomonocytic leukemic cells with MLL-fusion gene through the downregulation of Myc, thus providing insight into the development of novel therapeutic approaches.

Original languageEnglish
Pages (from-to)6749-6760
Number of pages12
JournalOncogene
Volume27
Issue number53
DOIs
Publication statusPublished - 2008 Nov 13
Externally publishedYes

Fingerprint

CCAAT-Enhancer-Binding Proteins
Gene Fusion
Cell Differentiation
Tretinoin
Acute Myeloid Leukemia
Down-Regulation
Myeloid Cells
Monocytes
Protein Isoforms
Leukemia
Up-Regulation

Keywords

  • Acute myeloid leukemia
  • CCAAT/enhancer binding protein-α
  • CCAAT/enhancer binding protein-ε
  • Mixed lineage leukemia gene
  • Monocytic differentiation

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Matsushita, H., Nakajima, H., Nakamura, Y., Tsukamoto, H., Tanaka, Y., Jin, G., ... Miyachi, H. (2008). C/EBPα and C/EBPε induce the monocytic differentiation of myelomonocytic cells with the MLL-chimeric fusion gene. Oncogene, 27(53), 6749-6760. https://doi.org/10.1038/onc.2008.285

C/EBPα and C/EBPε induce the monocytic differentiation of myelomonocytic cells with the MLL-chimeric fusion gene. / Matsushita, H.; Nakajima, H.; Nakamura, Y.; Tsukamoto, H.; Tanaka, Y.; Jin, G.; Yabe, M.; Asai, S.; Ono, R.; Nosaka, T.; Sugita, K.; Morimoto, A.; Hayashi, Y.; Hotta, T.; Ando, K.; Miyachi, H.

In: Oncogene, Vol. 27, No. 53, 13.11.2008, p. 6749-6760.

Research output: Contribution to journalArticle

Matsushita, H, Nakajima, H, Nakamura, Y, Tsukamoto, H, Tanaka, Y, Jin, G, Yabe, M, Asai, S, Ono, R, Nosaka, T, Sugita, K, Morimoto, A, Hayashi, Y, Hotta, T, Ando, K & Miyachi, H 2008, 'C/EBPα and C/EBPε induce the monocytic differentiation of myelomonocytic cells with the MLL-chimeric fusion gene', Oncogene, vol. 27, no. 53, pp. 6749-6760. https://doi.org/10.1038/onc.2008.285
Matsushita H, Nakajima H, Nakamura Y, Tsukamoto H, Tanaka Y, Jin G et al. C/EBPα and C/EBPε induce the monocytic differentiation of myelomonocytic cells with the MLL-chimeric fusion gene. Oncogene. 2008 Nov 13;27(53):6749-6760. https://doi.org/10.1038/onc.2008.285
Matsushita, H. ; Nakajima, H. ; Nakamura, Y. ; Tsukamoto, H. ; Tanaka, Y. ; Jin, G. ; Yabe, M. ; Asai, S. ; Ono, R. ; Nosaka, T. ; Sugita, K. ; Morimoto, A. ; Hayashi, Y. ; Hotta, T. ; Ando, K. ; Miyachi, H. / C/EBPα and C/EBPε induce the monocytic differentiation of myelomonocytic cells with the MLL-chimeric fusion gene. In: Oncogene. 2008 ; Vol. 27, No. 53. pp. 6749-6760.
@article{c5ec99aafc04490fbd6c447fb7c79363,
title = "C/EBPα and C/EBPε induce the monocytic differentiation of myelomonocytic cells with the MLL-chimeric fusion gene",
abstract = "CCAAT/enhancer binding proteins (C/EBPs) have an important function in granulocytic differentiation, and are also involved in the leukemogenesis of acute myeloid leukemia (AML). Their involvement in myelomonocytic leukemia, however, is still unclear. Therefore, the expression and function of C/EBPs in myelomonocytic cells with MLL-fusion genes were investigated. Retinoic acid (RA) induced monocytic differentiation in the myelomonocytic cell lines with MLL-fusion genes, THP-1, MOLM-14 and HF-6 cells, accompanied by monocytic differentiation with the upregulation of C/EBPα and C/EBPε. Monocytic differentiation by RA treatment was confirmed in primary AML cells using a clonogenic assay. When the activity of C/EBPα or C/EBPε was introduced into HF-6 cells, their cellular growth was arrested through differentiation into monocytes with the concomitant marked downregulation of Myc. Cebpe mRNA was upregulated by the induction of C/EBPα-ER, but not vice versa, thus suggesting that C/EBPε may have an important function in the differentiation process. Introduction of Myc isoforms into HF-6 cells partially antagonized the C/EBPs effects. These findings suggest that the ectopic expression of C/EBPε, as well as C/EBPα, can induce the monocytic differentiation of myelomonocytic leukemic cells with MLL-fusion gene through the downregulation of Myc, thus providing insight into the development of novel therapeutic approaches.",
keywords = "Acute myeloid leukemia, CCAAT/enhancer binding protein-α, CCAAT/enhancer binding protein-ε, Mixed lineage leukemia gene, Monocytic differentiation",
author = "H. Matsushita and H. Nakajima and Y. Nakamura and H. Tsukamoto and Y. Tanaka and G. Jin and M. Yabe and S. Asai and R. Ono and T. Nosaka and K. Sugita and A. Morimoto and Y. Hayashi and T. Hotta and K. Ando and H. Miyachi",
year = "2008",
month = "11",
day = "13",
doi = "10.1038/onc.2008.285",
language = "English",
volume = "27",
pages = "6749--6760",
journal = "Oncogene",
issn = "0950-9232",
publisher = "Nature Publishing Group",
number = "53",

}

TY - JOUR

T1 - C/EBPα and C/EBPε induce the monocytic differentiation of myelomonocytic cells with the MLL-chimeric fusion gene

AU - Matsushita, H.

AU - Nakajima, H.

AU - Nakamura, Y.

AU - Tsukamoto, H.

AU - Tanaka, Y.

AU - Jin, G.

AU - Yabe, M.

AU - Asai, S.

AU - Ono, R.

AU - Nosaka, T.

AU - Sugita, K.

AU - Morimoto, A.

AU - Hayashi, Y.

AU - Hotta, T.

AU - Ando, K.

AU - Miyachi, H.

PY - 2008/11/13

Y1 - 2008/11/13

N2 - CCAAT/enhancer binding proteins (C/EBPs) have an important function in granulocytic differentiation, and are also involved in the leukemogenesis of acute myeloid leukemia (AML). Their involvement in myelomonocytic leukemia, however, is still unclear. Therefore, the expression and function of C/EBPs in myelomonocytic cells with MLL-fusion genes were investigated. Retinoic acid (RA) induced monocytic differentiation in the myelomonocytic cell lines with MLL-fusion genes, THP-1, MOLM-14 and HF-6 cells, accompanied by monocytic differentiation with the upregulation of C/EBPα and C/EBPε. Monocytic differentiation by RA treatment was confirmed in primary AML cells using a clonogenic assay. When the activity of C/EBPα or C/EBPε was introduced into HF-6 cells, their cellular growth was arrested through differentiation into monocytes with the concomitant marked downregulation of Myc. Cebpe mRNA was upregulated by the induction of C/EBPα-ER, but not vice versa, thus suggesting that C/EBPε may have an important function in the differentiation process. Introduction of Myc isoforms into HF-6 cells partially antagonized the C/EBPs effects. These findings suggest that the ectopic expression of C/EBPε, as well as C/EBPα, can induce the monocytic differentiation of myelomonocytic leukemic cells with MLL-fusion gene through the downregulation of Myc, thus providing insight into the development of novel therapeutic approaches.

AB - CCAAT/enhancer binding proteins (C/EBPs) have an important function in granulocytic differentiation, and are also involved in the leukemogenesis of acute myeloid leukemia (AML). Their involvement in myelomonocytic leukemia, however, is still unclear. Therefore, the expression and function of C/EBPs in myelomonocytic cells with MLL-fusion genes were investigated. Retinoic acid (RA) induced monocytic differentiation in the myelomonocytic cell lines with MLL-fusion genes, THP-1, MOLM-14 and HF-6 cells, accompanied by monocytic differentiation with the upregulation of C/EBPα and C/EBPε. Monocytic differentiation by RA treatment was confirmed in primary AML cells using a clonogenic assay. When the activity of C/EBPα or C/EBPε was introduced into HF-6 cells, their cellular growth was arrested through differentiation into monocytes with the concomitant marked downregulation of Myc. Cebpe mRNA was upregulated by the induction of C/EBPα-ER, but not vice versa, thus suggesting that C/EBPε may have an important function in the differentiation process. Introduction of Myc isoforms into HF-6 cells partially antagonized the C/EBPs effects. These findings suggest that the ectopic expression of C/EBPε, as well as C/EBPα, can induce the monocytic differentiation of myelomonocytic leukemic cells with MLL-fusion gene through the downregulation of Myc, thus providing insight into the development of novel therapeutic approaches.

KW - Acute myeloid leukemia

KW - CCAAT/enhancer binding protein-α

KW - CCAAT/enhancer binding protein-ε

KW - Mixed lineage leukemia gene

KW - Monocytic differentiation

UR - http://www.scopus.com/inward/record.url?scp=56249118674&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=56249118674&partnerID=8YFLogxK

U2 - 10.1038/onc.2008.285

DO - 10.1038/onc.2008.285

M3 - Article

C2 - 18776924

AN - SCOPUS:56249118674

VL - 27

SP - 6749

EP - 6760

JO - Oncogene

JF - Oncogene

SN - 0950-9232

IS - 53

ER -