Everything you always wanted to know about cellular drug resistance in childhood acute lymphoblastic leukemia

Pieters, Rob; Klumper, E.; Kaspers, Gertjan J. L.; Veerman, A. J. P.

doi:10.1016/s1040-8428(96)00223-5

Cited by 52 publications

(36 citation statements)

References 108 publications

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“…In the two cases where patients were stratified by immunophenotype Kaspers et al, 2005), data from T-and B-lineage specimens were combined before analysis. Data for MPRED were available from only one study (Styczynski et al, 2002), Whilst MTX sensitivity cannot be measured in primary specimens using the MTT assay (Pieters et al, 1997).…”

Section: Comparison Of In Vitro and Ex Vivo Resistance Profilesmentioning

confidence: 99%

“…The experimental protocol (i.e. measurement by MTT assay after a 4-day drug incubation) was modelled on the approach successfully used to assess drug resistance in primary ALL bone marrow specimens ex vivo (Klumper et al, 1995;Kaspers et al, 1997Kaspers et al, , 2005. For most drugs, sensitivities ranged over several orders of magnitude.…”

Section: Cell Line Drug Resistance Profilesmentioning

confidence: 99%

“…This is true not only for relapsed ALL (Klumper et al, 1995) where in vivo selection of resistant clones occurs during therapy, but also in those newly diagnosed with the disease (Kaspers et al, 1997;Pieters et al, 1998). Much of our knowledge of the resistance phenotypes in ALL has been derived using isolated bone marrow specimens studied in short-term culture using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay.…”

mentioning

confidence: 99%

“…However, application of this ex vivo approach for functional studies or drug screening is limited by both the availability of patient material and the short period of survival of these cells in culture. Furthermore, this approach cannot be used to measure methotrexate (MTX) resistance in such specimens because the high rate of spontaneous cell death releases nucleosides in sufficient quantity to prevent MTX cytotoxicity (Pieters et al, 1997). Investigation of resistance mechanisms and evaluation of novel drug-leads invariably requires the use of immortalised cell lines, but the extent to which these cells retain features of the original disease in vivo is a matter of some debate (Kamb, 2005), a problem exemplified by the typically high growth rates of continuous cultures (Masters, 2000).…”

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confidence: 99%

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Authenticity and drug resistance in a panel of acute lymphoblastic leukaemia cell lines

et al. 2006

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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 48000-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.

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Section: Comparison Of In Vitro and Ex Vivo Resistance Profilesmentioning

confidence: 99%

Section: Cell Line Drug Resistance Profilesmentioning

confidence: 99%

mentioning

confidence: 99%

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confidence: 99%

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Authenticity and drug resistance in a panel of acute lymphoblastic leukaemia cell lines

et al. 2006

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“…The assay results correlate with clinical and cell biological features, as well as with clinical outcome after single agent and after combination chemotherapy. [14][15][16][17][18][19][20][21][22][23][24][25][26] To determine the potential of aplidin as a cytotoxic agent in pediatric leukemia, we have tested bone marrow (BM) and peripheral blood (PB) samples of children with different types of leukemia and of children without leukemia in the MTT assay and compared the results with in vitro cytotoxicity of known antileukemic agents.…”

Section: Introductionmentioning

confidence: 99%

In vitro cytotoxicity of aplidin and crossresistance with other cytotoxic drugs in childhood leukemic and normal bone marrow and blood samples: a rational basis for clinical development

et al. 2003

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To determine the potential of aplidin as a cytotoxic agent in pediatric leukemia, we tested bone marrow (BM) and peripheral blood (PB) samples (n ¼ 72) of children with different types of leukemia and healthy children in the methyl-thiazol-tetrazolium assay. Also, we compared these results with other cytotoxic drugs. Aplidin was cytotoxic in vitro at nanomolar concentrations, in a dose-dependent fashion. L-carnitine, that is applied in clinical studies to prevent myotoxicity caused by aplidin, had no effect on aplidin cytotoxicity in vitro. Aplidin cytotoxicity in vitro was not different when initial and relapsed acute lymphoblastic leukemia (ALL) or initial ALL and initial acute myeloid leukemia were compared. However, normal BM (n ¼ 19) and PB (n ¼ 13) cells were more resistant to aplidin than leukemic cells (median two-to seven-fold, P ¼ 0.001 and median four-to 11-fold, Po0.0001, respectively). In leukemia samples, no significant crossresistance between aplidin and other cytotoxic drugs was found, except for a trend for correlation with 2 0 ,2 0 -difluorodeoxycytidine (q ¼ 0.71, P ¼ 0.02). In normal BM samples, significant crossresistance with the epipodophyllotoxins was found, which is not readily explained by the currently known mechanisms of action of aplidin. In conclusion, we show that aplidin has selective cytotoxicity in vitro towards childhood leukemia cells and generally lacks crossresistance with other known cytotoxic drugs, which warrants clinical studies.

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Unusual η²‐Allene Osmacycle with Apoptotic Properties

Gong

Kräling

et al. 2010

ChemBioChem

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Screening of a library of structurally unusual osmacyclic complexes for their antiproliferate properties in HeLa cells led to the discovery of a highly cytotoxic eta2-allene osmacycle. In this remarkably stable complex, osmium constitutes part of a metallacycle through the formation of a sigma-bond to a carbon in combination with coordination to an allene moiety. The osmacycle strongly induces apoptosis in Burkitt-like lymphoma cells at submicromolar concentrations. The reduction of the mitochondrial membrane potential, the induction of DNA fragmentation, and the activation of caspases-9 and -3 reveal that programmed cell death occurs through the intrinsic mitochondrial pathway. From the lipophilic and cationic nature of the osmacycle, in addition to a low oxidation potential (E1/2=+0.27 V vs. Fc/Fc+, Fc=ferrocene) it is proposed that mitochondria are the cellular target where oxidative decomposition initiates apoptosis.

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Everything you always wanted to know about cellular drug resistance in childhood acute lymphoblastic leukemia

Cited by 52 publications

References 108 publications

Authenticity and drug resistance in a panel of acute lymphoblastic leukaemia cell lines

Authenticity and drug resistance in a panel of acute lymphoblastic leukaemia cell lines

In vitro cytotoxicity of aplidin and crossresistance with other cytotoxic drugs in childhood leukemic and normal bone marrow and blood samples: a rational basis for clinical development

Unusual η²‐Allene Osmacycle with Apoptotic Properties

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Everything you always wanted to know about cellular drug resistance in childhood acute lymphoblastic leukemia

Cited by 52 publications

References 108 publications

Authenticity and drug resistance in a panel of acute lymphoblastic leukaemia cell lines

Authenticity and drug resistance in a panel of acute lymphoblastic leukaemia cell lines

In vitro cytotoxicity of aplidin and crossresistance with other cytotoxic drugs in childhood leukemic and normal bone marrow and blood samples: a rational basis for clinical development

Unusual η2‐Allene Osmacycle with Apoptotic Properties

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Unusual η²‐Allene Osmacycle with Apoptotic Properties