Cellular drug sensitivity in MLL-rearranged childhood acute leukaemia is correlated to partner genes and cell lineage

2.50
Hdl Handle:
http://hdl.handle.net/2336/53773
Title:
Cellular drug sensitivity in MLL-rearranged childhood acute leukaemia is correlated to partner genes and cell lineage
Authors:
Palle, J; Frost, B M; Forestier, E; Gustafsson, G; Nygren, P; Hellebostad, M; Jonsson, O G; Kanerva, J; Schmiegelow, K; Larsson, R; Lönnerholm, G
Citation:
Br. J. Haematol. 2005, 129(2):189-98
Issue Date:
1-Apr-2005
Abstract:
Rearrangements in the 11q23 region, the site of the mixed lineage leukaemia (MLL) gene, are found in both childhood acute myeloid (AML) and lymphoblastic (ALL) leukaemia. We studied the in vitro drug resistance by the fluorometric microculture cytotoxicity assay (FMCA) in 132 children with AML and 178 children with ALL (aged 0-17 years). In AML, children with t(9;11) (n = 10) were significantly more sensitive to cytarabine (P < 0.001) and doxorubicin (P = 0.005) than non-11q23 rearranged patients (n = 108). Children with other 11q23 rearrangements (n = 14) differed less from non-rearranged children. The 'AML-profile' common to all three groups included relative resistance to glucocorticoids and vincristine. In ALL, children with 11q23 rearrangement (n = 22) were significantly more sensitive to cytarabine (P = 0.026) than children without 11q23 rearrangement (n = 156), also after stratification for white blood cell count. In conclusion, the findings indicate that the cellular drug resistance is correlated to both the cell lineage and the type of 11q23 rearrangement. High cellular sensitivity to cytarabine and doxorubicin might explain the excellent treatment results in children with AML and t(9;11). The present study supports the strategy of contemporary protocols to include high-dose cytarabine in the treatment of 11q23-positive patients both in AML and ALL.
Description:
To access publisher full text version of this article. Please click on the hyperlink in Additional Links field
Additional Links:
http://dx.doi.org/10.1111/j.1365-2141.2005.05433.x

Full metadata record

DC FieldValue Language
dc.contributor.authorPalle, J-
dc.contributor.authorFrost, B M-
dc.contributor.authorForestier, E-
dc.contributor.authorGustafsson, G-
dc.contributor.authorNygren, P-
dc.contributor.authorHellebostad, M-
dc.contributor.authorJonsson, O G-
dc.contributor.authorKanerva, J-
dc.contributor.authorSchmiegelow, K-
dc.contributor.authorLarsson, R-
dc.contributor.authorLönnerholm, G-
dc.date.accessioned2009-03-10T13:06:32Z-
dc.date.available2009-03-10T13:06:32Z-
dc.date.issued2005-04-01-
dc.date.submitted2009-03-10-
dc.identifier.citationBr. J. Haematol. 2005, 129(2):189-98en
dc.identifier.issn0007-1048-
dc.identifier.pmid15813846-
dc.identifier.doi10.1111/j.1365-2141.2005.05433.x-
dc.identifier.urihttp://hdl.handle.net/2336/53773-
dc.descriptionTo access publisher full text version of this article. Please click on the hyperlink in Additional Links fielden
dc.description.abstractRearrangements in the 11q23 region, the site of the mixed lineage leukaemia (MLL) gene, are found in both childhood acute myeloid (AML) and lymphoblastic (ALL) leukaemia. We studied the in vitro drug resistance by the fluorometric microculture cytotoxicity assay (FMCA) in 132 children with AML and 178 children with ALL (aged 0-17 years). In AML, children with t(9;11) (n = 10) were significantly more sensitive to cytarabine (P < 0.001) and doxorubicin (P = 0.005) than non-11q23 rearranged patients (n = 108). Children with other 11q23 rearrangements (n = 14) differed less from non-rearranged children. The 'AML-profile' common to all three groups included relative resistance to glucocorticoids and vincristine. In ALL, children with 11q23 rearrangement (n = 22) were significantly more sensitive to cytarabine (P = 0.026) than children without 11q23 rearrangement (n = 156), also after stratification for white blood cell count. In conclusion, the findings indicate that the cellular drug resistance is correlated to both the cell lineage and the type of 11q23 rearrangement. High cellular sensitivity to cytarabine and doxorubicin might explain the excellent treatment results in children with AML and t(9;11). The present study supports the strategy of contemporary protocols to include high-dose cytarabine in the treatment of 11q23-positive patients both in AML and ALL.en
dc.language.isoenen
dc.publisherBlackwell Scientific Publicationsen
dc.relation.urlhttp://dx.doi.org/10.1111/j.1365-2141.2005.05433.xen
dc.subject.meshAcute Diseaseen
dc.subject.meshAdolescenten
dc.subject.meshAntineoplastic Agentsen
dc.subject.meshCell Lineageen
dc.subject.meshChilden
dc.subject.meshChild, Preschoolen
dc.subject.meshChromosomes, Human, Pair 11en
dc.subject.meshChromosomes, Human, Pair 9en
dc.subject.meshCytarabineen
dc.subject.meshCytotoxicity Tests, Immunologicen
dc.subject.meshDNA-Binding Proteinsen
dc.subject.meshDoxorubicinen
dc.subject.meshDrug Resistance, Neoplasmen
dc.subject.meshFemaleen
dc.subject.meshFluorometryen
dc.subject.meshGene Rearrangementen
dc.subject.meshGlucocorticoidsen
dc.subject.meshHumansen
dc.subject.meshInfanten
dc.subject.meshInfant, Newbornen
dc.subject.meshLeukemia, Myeloiden
dc.subject.meshMaleen
dc.subject.meshMyeloid-Lymphoid Leukemia Proteinen
dc.subject.meshPrecursor Cell Lymphoblastic Leukemia-Lymphomaen
dc.subject.meshProspective Studiesen
dc.subject.meshProto-Oncogenesen
dc.subject.meshStatistics, Nonparametricen
dc.subject.meshTranscription Factorsen
dc.subject.meshTranslocation, Geneticen
dc.titleCellular drug sensitivity in MLL-rearranged childhood acute leukaemia is correlated to partner genes and cell lineageen
dc.typeArticleen
dc.contributor.departmentDepartment of Women's and Children's Health, University Children's Hospital, Uppsala, Sweden. josefine.palle@akademiska.seen
dc.identifier.journalBritish journal of haematologyen

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