p210 Bcr-Abl expression in a primitive multipotent haematopoietic cell line models the development of chronic myeloid leukaemia.
Affiliation
Leukaemia Research Fund Cellular Development Unit, UMIST, Manchester, UK.Issue Date
1998-08-06
Metadata
Show full item recordAbstract
Chronic myeloid leukaemia (CML) is a clonal disorder of the pluripotent haemopoietic stem cell, the hallmark of which is the constitutively activated Bcr-Abl protein tyrosine kinase. During the initial chronic phase of CML the primitive multipotent leukaemic progenitor cells remain growth factor dependent and are capable of producing terminally differentiated cells. Although the available evidence suggests that Bcr-Abl directly affects signalling pathways involved in controlling the development of primitive haemopoietic progenitors the identification of the specific biological consequences of Bcr-Abl activity in these progenitors has been hampered by the lack of suitable systems modelling CML. By transfecting the multipotent haemopoietic cell line FDCP-Mix with a temperature sensitive mutant of Bcr-Abl we have developed the first working model that mirrors the chronic phase of CML. FDCP-Mix cells expressing Bcr-Abl tyrosine kinase activity remain growth factor dependent and retain their ability to differentiate. Normal neutrophilic cells are formed in response to G-CSF and GM-CSF. In addition, the transfected FDCP-Mix cells grown at the permissive temperature for Bcr-Abl tyrosine kinase activity display enhanced survival and proliferation in low concentrations of growth factor. These findings are consistent with the initial subtle changes seen in CML progenitor cells during the chronic phase and confirm that Bcr-Abl effects are context specific, i.e. they depend on the origin and developmental potential of the transfected cells. This questions the significance of studies in non-haemopoietic and differentiation blocked haemopoietic cells.Citation
p210 Bcr-Abl expression in a primitive multipotent haematopoietic cell line models the development of chronic myeloid leukaemia. 1998, 17 (5):667-72 OncogeneJournal
OncogeneDOI
10.1038/sj.onc.1201969PubMed ID
9704934Type
ArticleLanguage
enISSN
0950-9232ae974a485f413a2113503eed53cd6c53
10.1038/sj.onc.1201969
Scopus Count
Collections
Related articles
- Upregulation of the TGFbeta signalling pathway by Bcr-Abl: implications for haemopoietic cell growth and chronic myeloid leukaemia.
- Authors: Møller GM, Frost V, Melo JV, Chantry A
- Issue date: 2007 Apr 3
- Abl protein kinase abrogates the response of multipotent haemopoietic cells to the growth inhibitor macrophage inflammatory protein-1 alpha.
- Authors: Wark G, Heyworth CM, Spooncer E, Czaplewski L, Francis JM, Dexter TM, Whetton AD
- Issue date: 1998 Mar 12
- BCR-ABL alters the proliferation and differentiation response of multipotent hematopoietic cells to stem cell factor.
- Authors: Pierce A, Spooncer E, Ainsworth S, Whetton AD
- Issue date: 2002 May 2
- Bcr-Abl protein tyrosine kinase activity induces a loss of p53 protein that mediates a delay in myeloid differentiation.
- Authors: Pierce A, Spooncer E, Wooley S, Dive C, Francis JM, Miyan J, Owen-Lynch PJ, Dexter TM, Whetton AD
- Issue date: 2000 Nov 16
- Effect of mutational inactivation of tyrosine kinase activity on BCR/ABL-induced abnormalities in cell growth and adhesion in human hematopoietic progenitors.
- Authors: Ramaraj P, Singh H, Niu N, Chu S, Holtz M, Yee JK, Bhatia R
- Issue date: 2004 Aug 1