Establishment of a pluripotent preleukaemic stem cell line by expression of the AML1-ETO fusion protein in Notch1-immortalized HSCN1cl10 cells.
The AML1-ETO fusion has been associated with up to 40% of acute myeloid leukaemia French-American-British classified M2 cases. This chimaeric protein interferes with normal AML1 function and disrupts critical transcriptional regulation of haematopoiesis. Current evidence suggests that AML1-ETO alone is insufficient to induce leukaemia, but rather is a co-operating event in leukaemogenesis. We developed a pluripotent murine haematopoietic stem cell line expressing the AML1-ETO fusion protein that displays in vitro and in vivo properties consistent with a preleukaemic state, including inhibition of terminal granulocytic differentiation in vitro and the development of non-lymphoid leukaemias in vivo. This cell line represents a potential platform for the introduction and in vitro rapid screening of candidate genes thought to co-operate with AML1-ETO in developing frank leukaemia.
Delaney
Colleen
C
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. sdelaney@fhcrc.org
Bernstein
Irwin D
ID
D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D050676:Core Binding Factor Alpha 2 Subunit; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D051379:Mice; D009363:Neoplasm Proteins / Q000378:metabolism; D009368:Neoplasm Transplantation; D015514:Oncogene Proteins, Fusion / Q000378:metabolism*; D039904:Pluripotent Stem Cells / Q000378:metabolism*; D011289:Preleukemia / Q000235:genetics / Q000378:metabolism*; D000075142:RUNX1 Translocation Partner 1 Protein; D014157:Transcription Factors / Q000378:metabolism*; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured
C107844:AML1-ETO fusion protein, human; D050676:Core Binding Factor Alpha 2 Subunit; D009363:Neoplasm Proteins; D015514:Oncogene Proteins, Fusion; D000075142:RUNX1 Translocation Partner 1 Protein; D014157:Transcription Factors