<i>In vitro</i> drug resistance profiles of adult versus childhood acute lymphoblastic leukaemia

Styczyński, Jan; Pieters, Rob; Huismans, D. R.; Schuurhuis, Gerrit Jan; Wysocki, M; Veerman, A. J. P.

doi:10.1046/j.1365-2141.2000.02211.x

Cited by 53 publications

(40 citation statements)

References 31 publications

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“…Data from multiple studies (Pieters et al, 1990(Pieters et al, , 1991Klumper et al, 1995;Duyn et al, 1999;Styczynski et al, 2000Styczynski et al, , 2002Styczynski et al, , 2005Zwaan et al, 2000;Mihal et al, 2004;Fine et al, 2005;Kaspers et al, 2005;Steinbach et al, 2005) were combined to determine an absolute minimum and maximum IC 50 range for bone marrow specimens obtained from paediatric ALL patients at the time of diagnosis (PD) or relapse (PR). Data reported in these studies as LC 50 values are, for simplicity, referred to here in terms of IC 50 .…”

Section: Comparison Of In Vitro and Ex Vivo Resistance Profilesmentioning

confidence: 99%

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%

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

et al. 2006

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“…Short-term cultures have been used to explore conditions for the proliferation and cytoreduction of T-ALL cells. [5][6][7][8][9] Although immortalized cell lines derived from T-ALL cells have also been useful in characterizing the cell growth pattern, 10,11 they may not be suitable for an observation of T-ALL cells that mimic the overall growth pattern in a living body.…”

Section: Introductionmentioning

confidence: 99%

Growth of human T cell acute lymphoblastic leukemia lymphoblasts in NOD/SCID mouse fetal thymus organ culture

et al. 2002

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The in vitro proliferation of T cell acute lymphoblastic leukemia (T-ALL) cells in its entirety has not been well delineated because of a lack of an appropriate culture system that mimics the growth pattern in a living body. We applied a NOD/SCID mouse fetal thymus organ culture (FTOC) for leukemic cells from fresh (one case) and frozen (seven cases) bone marrow (BM) samples of children with T-ALL. Cell growth was observed in all seven samples in the culture, reaching a proliferational peak at 4 weeks, and it was calculated that the proliferation potential was 212-to 319-fold. The FTOC-derived T-ALL cells showed similarity to the original cells morphologically and immunophenotypically, still possessed clonalities and were able to regenerate overt leukemia in NOD/SCID mice. These FTOC-derived T-ALL cells differed from ordinary cell lines because they always need FTOC support. Thus, we established a new in vitro culture for T-ALL cells. A comparison of the original and FTOC-derived T-ALL cells revealed that the proportion of cells expressing IL-7R increased in all seven cases. Sorting and re-seeding of FTOC-derived IL-7R+ and IL-7R؊ cells into

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“…This may be caused by unfavorable cytogenetic of leukemic cells, lack of expected pharmacokinetics, cellular drug resistance, pharmacological resistance, and the persistence of minimal residual disease [5,14,15]. Cellular drug resistance is supposed to play a major role in chemotherapy failures of both newly diagnosed cases and relapse cases of acute leukemia [8,9]. A more detailed insight regarding drug resistance may be used as a rationale to develop more effective treatment regimens for such patients.…”

Section: Discussionmentioning

confidence: 99%

“…Compared with other in vitro chemosensitivity tests, the MTT assay is a short-term assay (2-4 days) and uses a very low number of cells in suspension. Because of its high efficiency, the assay is currently used in determining the chemosensitivity of cell lines [4][5][6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Relationship between In Vitro Chemosensitivity assessed with MTT Assay and Clinical Outcomes in 103 Patients with Acute Leukemia

et al. 2007

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Background : Cellular drug resistance is supposed to play a major role in chemotherapy failure or relapse. The purpose of this study was to analyze the relationship between in vitro chemosensitivity test results using a 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and clinical response on chemotherapy, and to find the possibility of optimizing the treatment protocol for individual patients according to their actual drug resistance.Methods : For MTT assay, we obtained bone marrow aspirates from 103 patients with acute leukemia at the time of initial diagnosis or relapse. The following drugs were tested: cytarabine, vincristine, methotrexate, daunorubicin, dexamethasone, L-asparaginase, and mitoxantrone. To evaluate clinical responses after induction chemotherapy, we followed up on their bone marrow study.Results : In our study, in vitro chemosensitivity test with the MTT assay significantly predicted whether patients with AML remained continuous complete remission or went into relapse. It also predicted whether or not child patients with ALL would acquire complete remission after induction chemotherapy.Conclusions : Although it does not provide the insight into the mechanisms that cause drug resistance, the MTT assay may be a useful tool in individually optimizing the chemotherapy of patients with acute leukemia. (Korean J Lab Med 2007;27:89-95)

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In vitro drug resistance profiles of adult versus childhood acute lymphoblastic leukaemia

Cited by 53 publications

References 31 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

Growth of human T cell acute lymphoblastic leukemia lymphoblasts in NOD/SCID mouse fetal thymus organ culture

Relationship between In Vitro Chemosensitivity assessed with MTT Assay and Clinical Outcomes in 103 Patients with Acute Leukemia

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