p210 Bcr-Abl expression in a primitive multipotent haematopoietic cell line models the development of chronic myeloid leukaemia.

2.50
Hdl Handle:
http://hdl.handle.net/10541/92726
Title:
p210 Bcr-Abl expression in a primitive multipotent haematopoietic cell line models the development of chronic myeloid leukaemia.
Authors:
Pierce, A; Owen-Lynch, P J; Spooncer, Elaine; Dexter, T Michael; Whetton, Anthony D
Abstract:
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.
Affiliation:
Leukaemia Research Fund Cellular Development Unit, UMIST, Manchester, UK.
Citation:
p210 Bcr-Abl expression in a primitive multipotent haematopoietic cell line models the development of chronic myeloid leukaemia. 1998, 17 (5):667-72 Oncogene
Journal:
Oncogene
Issue Date:
6-Aug-1998
URI:
http://hdl.handle.net/10541/92726
DOI:
10.1038/sj.onc.1201969
PubMed ID:
9704934
Type:
Article
Language:
en
ISSN:
0950-9232
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorPierce, Aen
dc.contributor.authorOwen-Lynch, P Jen
dc.contributor.authorSpooncer, Elaineen
dc.contributor.authorDexter, T Michaelen
dc.contributor.authorWhetton, Anthony Den
dc.date.accessioned2010-02-23T13:26:48Z-
dc.date.available2010-02-23T13:26:48Z-
dc.date.issued1998-08-06-
dc.identifier.citationp210 Bcr-Abl expression in a primitive multipotent haematopoietic cell line models the development of chronic myeloid leukaemia. 1998, 17 (5):667-72 Oncogeneen
dc.identifier.issn0950-9232-
dc.identifier.pmid9704934-
dc.identifier.doi10.1038/sj.onc.1201969-
dc.identifier.urihttp://hdl.handle.net/10541/92726-
dc.description.abstractChronic 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.en
dc.language.isoenen
dc.subjectHaematopoietic Stem Cellsen
dc.subjectLeukaemiaen
dc.subject.meshCell Division-
dc.subject.meshCell Line-
dc.subject.meshCell Survival-
dc.subject.meshFusion Proteins, bcr-abl-
dc.subject.meshHematopoietic Stem Cells-
dc.subject.meshHumans-
dc.subject.meshLeukemia, Myelogenous, Chronic, BCR-ABL Positive-
dc.subject.meshModels, Biological-
dc.subject.meshTemperature-
dc.titlep210 Bcr-Abl expression in a primitive multipotent haematopoietic cell line models the development of chronic myeloid leukaemia.en
dc.typeArticleen
dc.contributor.departmentLeukaemia Research Fund Cellular Development Unit, UMIST, Manchester, UK.en
dc.identifier.journalOncogeneen

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