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Authenticity and drug resistance in a panel of acute lymphoblastic leukaemia cell lines
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Authenticity and drug resistance in a panel of acute lymphoblastic leukaemia cell lines
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Journal Article
Authenticity and drug resistance in a panel of acute lymphoblastic leukaemia cell lines
2006
Overview
Cell lines are important models for drug resistance in acute lymphoblastic leukaemia (ALL), but are often criticised as being unrepresentative of primary disease. There are also doubts regarding the authenticity of many lines. We have characterised a panel of ALL cell lines for growth and drug resistance and compared data with that published for primary patient specimens. In contrast to the convention that cell lines are highly proliferative, those established in our laboratory grow at rates similar to estimates of leukaemic cells
in vivo
(doubling time 53–442 h). Authenticity was confirmed by genetic fingerprinting, which also demonstrated the potential stability of long-term cultures.
In vitro
glucocorticoid resistance correlated well with that measured
ex vivo
, but all lines were significantly more sensitive to vincristine than primary specimens. Sensitivity to methotrexate was inversely correlated to that of glucocorticoids and
L
-asparaginase, indicating possible reciprocity in resistance mechanisms. A cell line identified as highly methotrexate resistant (IC
50
>8000-fold higher than other lines) was derived from a patient receiving escalating doses of the drug, indicating
in vivo
selection of resistance as a cause of relapse. Many of these lines are suitable as models to study naturally occurring resistance phenotypes in paediatric ALL.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
Antineoplastic Agents - pharmacology
/ Biological and medical sciences
/ Biomedical and Life Sciences
/ Cell Line, Tumor - drug effects
/ Child
/ Hematologic and hematopoietic diseases
/ Humans
/ Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis
/ Oncology
/ Precursor Cell Lymphoblastic Leukemia-Lymphoma
/ Tumors
