Mutants of a multipotent hematopoietic cell line blocked in GM-CSF-induced differentiation are leukemogenic in vivo.
AffiliationPaterson Institute for Cancer Research, Manchester, UK.
MetadataShow full item record
AbstractFDCP-Mix cells infected with a retroviral vector expressing the GM-CSF gene (GMV-FDCP-Mix) self-renew in the presence of interleukin-3 (IL-3), are multipotent, and undergo differentiation into granulocytes and macrophages coupled with clonal extinction after removal of IL-3. Mutants of GMV-FDCP-Mix were isolated that escape clonal extinction after differentiation induction by the autocrine secreted GM-CSF. Some of these mutant clones have a blast cell morphology and are blocked in differentiation, whereas others exhibit all stages of granulocyte and macrophage differentiation without clonal extinction. In contrast to the parental GMV-FDCP-Mix cells, all the mutants tested were leukemogenic when injected into syngeneic mice. Depending on the in vitro differentiation capacity of the transplanted mutant cell lines, the animals developed undifferentiated blast cell leukemias or CML-like syndromes. Thus, these mutant cell lines can be used to define the cooperating steps in autocrine myeloid leukemia.
CitationMutants of a multipotent hematopoietic cell line blocked in GM-CSF-induced differentiation are leukemogenic in vivo. 1994, 22 (9):933-40 Exp. Hematol.
- Transcriptional regulation of the c-fms proto-oncogene mediated by granulocyte/macrophage colony-stimulating factor (GM-CSF) in murine cell lines.
- Authors: Helftenbein G, Krusekopf K, Just U, Cross M, Ostertag W, Niemann H, Tamura T
- Issue date: 1996 Feb 15
- Identification of primary structural features that define the differential actions of IL-3 and GM-CSF receptors.
- Authors: Evans CA, Ariffin S, Pierce A, Whetton AD
- Issue date: 2002 Nov 1
- In vitro induction of inhibitory macrophage differentiation by granulocyte-macrophage colony-stimulating factor, stem cell factor and interferon-gamma from lineage phenotypes-negative c-kit-positive murine hematopoietic progenitor cells.
- Authors: Ferret-Bernard S, Saï P, Bach JM
- Issue date: 2004 Feb 15
- Primitive interleukin 3 null hematopoietic cells transduced with BCR-ABL show accelerated loss after culture of factor-independence in vitro and leukemogenic activity in vivo.
- Authors: Jiang X, Ng E, Yip C, Eisterer W, Chalandon Y, Stuible M, Eaves A, Eaves CJ
- Issue date: 2002 Nov 15