Malignant Transformation Initiated by Mll-AF9: Gene Dosage and Critical Target Cells

Weili Chen, Ashish R. Kumar, Wendy A. Hudson, Quanzhi Li, Baolin Wu, Rodney A. Staggs, Erik A. Lund, Thien N. Sam, John H. Kersey

Research output: Contribution to journalArticle

160 Scopus citations

Abstract

The pathways by which oncogenes, such as MLL-AF9, initiate transformation and leukemia in humans and mice are incompletely defined. In a study of target cells and oncogene dosage, we found that Mll-AF9, when under endogenous regulatory control, efficiently transformed LSK (Lin-Sca1+c-kit+) stem cells, while committed granulocyte-monocyte progenitors (GMPs) were transformation resistant and did not cause leukemia. Mll-AF9 was expressed at higher levels in hematopoietic stem (HSC) than GMP cells. Mll-AF9 gene dosage effects were directly shown in experiments where GMPs were efficiently transformed by the high dosage of Mll-AF9 resulting from retroviral transduction. Mll-AF9 upregulated expression of 192 genes in both LSK and progenitor cells, but to higher levels in LSKs than in committed myeloid progenitors.

Original languageEnglish (US)
Pages (from-to)432-440
Number of pages9
JournalCancer Cell
Volume13
Issue number5
DOIs
StatePublished - May 6 2008

Keywords

  • CELLCYCLE

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    Chen, W., Kumar, A. R., Hudson, W. A., Li, Q., Wu, B., Staggs, R. A., Lund, E. A., Sam, T. N., & Kersey, J. H. (2008). Malignant Transformation Initiated by Mll-AF9: Gene Dosage and Critical Target Cells. Cancer Cell, 13(5), 432-440. https://doi.org/10.1016/j.ccr.2008.03.005