Id1 immortalizes hematopoietic progenitors in vitro and promotes a myeloproliferative disease in vivo

H. C. Suh, W. Leeanansaksiri, M. Ji, K. D. Klarmann, K. Renn, J. Gooya, D. Smith, I. McNiece, S. Lugthart, P. J.M. Valk, R. Delwel, J. R. Keller

Research output: Contribution to journalArticle

Abstract

Id1 is frequently overexpressed in many cancer cells, but the functional significance of these findings is not known. To determine if Id1 could contribute to the development of hematopoietic malignancy, we reconstituted mice with hematopoietic cells overexpressing Id1. We showed for the first time that deregulated expression of Id1 leads to a myeloproliferative disease in mice, and immortalizes myeloid progenitors in vitro. In human cells, we demonstrate that Id genes are expressed in human acute myelogenous leukemia cells, and that knock down of Id1 expression inhibits leukemic cell line growth, suggesting that Id1 is required for leukemic cell proliferation. These findings established a causal relationship between Id1 overexpression and hematologic malignancy. Thus, deregulated expression of Id1 may contribute to the initiation of myeloid malignancy, and Id1 may represent a potential therapeutic target for early stage intervention in the treatment of hematopoietic malignancy.

Original languageEnglish (US)
Pages (from-to)5612-5623
Number of pages12
JournalOncogene
Volume27
Issue number42
DOIs
StatePublished - Sep 18 2008

Keywords

  • Id1
  • Leukemia
  • Myeloproliferative disease
  • Prevention
  • Therapeutic target

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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    Suh, H. C., Leeanansaksiri, W., Ji, M., Klarmann, K. D., Renn, K., Gooya, J., Smith, D., McNiece, I., Lugthart, S., Valk, P. J. M., Delwel, R., & Keller, J. R. (2008). Id1 immortalizes hematopoietic progenitors in vitro and promotes a myeloproliferative disease in vivo. Oncogene, 27(42), 5612-5623. https://doi.org/10.1038/onc.2008.175